Peptide nucleic acid combinatorial libraries and improved methods of synthesis

Claim 1

A method of adding further peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) treating said oligomer having said extension thereon with an acetylnucleobase synthon to form an amide bond between said acetylnucleobase synthon and said secondary amine of said extension forming a new protected amine terminated resin bound peptide nucleic acid oligomer; e) deprotecting said protected amino group of said resin bound extended oligomer; and f) repeating steps a-e to further extend said oligomer; or g) terminating said synthesis.

Claim 2

A method of adding further peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) treating said oligomer having said extension thereon with an acetylnucleobase synthon to form an amide bond between said acetylnucleobase synthon and said secondary amine of said extension forming a new protected amine terminated resin bound peptide nucleic acid oligomer; e) deprotecting said protected amino group of said resin bound extended oligomer; and f) repeating steps a-e to further extend said oligomer; or g) terminating said synthesis.

Claim 15

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound peptide nucleic acid oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound peptide nucleic acid oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound peptide nucleic acid oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) selecting a plurality of acetylnucleobase synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; e) treating said resin bound peptide nucleic acid oligomer having said extension thereon with said plurality of acetylnucleobase synthons to form an amide bond between an acetylnucleobase synthon and said secondary amine of said extension to extend said peptide nucleic acid oligomer with a new protected amine terminated resin bound peptide nucleic acid unit connected to other preceding peptide nucleic acid units; f) deprotecting said protected amino group of said resin bound peptide nucleic acid unit to extend said peptide nucleic acid oligomer; and g) repeating steps a-f to further extend said oligomer; or h) terminating said synthesis.

Claim 16

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound peptide nucleic acid oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound peptide nucleic acid oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound peptide nucleic acid oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) selecting a plurality of acetylnucleobase synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; e) treating said resin bound peptide nucleic acid oligomer having said extension thereon with said plurality of acetylnucleobase synthons to form an amide bond between an acetylnucleobase synthon and said secondary amine of said extension to extend said peptide nucleic acid oligomer with a new protected amine terminated resin bound peptide nucleic acid unit connected to other preceding peptide nucleic acid units; f) deprotecting said protected amino group of said resin bound peptide nucleic acid unit to extend said peptide nucleic acid oligomer; and g) repeating steps a-f to further extend said oligomer; or h) terminating said synthesis.

Claim 20

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) dividing said resin into portions; e) selecting a plurality of acetylnucleobase synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; f) treating each of said portions of said resin bound oligomer having said extension thereon with one of said acetylnucleobase synthons to form an amide bond between the acetylnucleobase synthon and said secondary amine of said extension to extend said oligomer by the addition of a new protected amine terminated peptide nucleic acid unit connected to said oligomer; g) combining each of said portions of resin together; h) deprotecting said protected amino group of said resin bound peptide nucleic acid oligomer; and i) repeating steps a-h to further extend said oligomer; or j) terminating said synthesis.

Claim 21

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) dividing said resin into portions; e) selecting a plurality of acetylnucleobase synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; f) treating each of said portions of said resin bound oligomer having said extension thereon with one of said acetylnucleobase synthons to form an amide bond between the acetylnucleobase synthon and said secondary amine of said extension to extend said oligomer by the addition of a new protected amine terminated peptide nucleic acid unit connected to said oligomer; g) combining each of said portions of resin together; h) deprotecting said protected amino group of said resin bound peptide nucleic acid oligomer; and i) repeating steps a-h to further extend said oligomer; or j) terminating said synthesis.

Claim 25

A method of adding peptide nucleic acid units to one of an amine terminated peptide nucleic acid oligomer or an amine terminated amino acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) treating said oligomer having said extension thereon with an acetylnucleobase synthon to form an amide bond between said acetylnucleobase synthon and said secondary amine of said extension forming a new protected amine terminated resin bound peptide nucleic acid oligomer; e) deprotecting said protected amino group of said resin bound extended oligomer; and f) repeating steps a-e to further extend said oligomer; or g) terminating said synthesis.

Claim 26

A method of adding peptide nucleic acid units to one of an amine terminated peptide nucleic acid oligomer or an amine terminated amino acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound oligomer having an extension thereon where said extension includes a secondary amine and a protected amino group; d) treating said oligomer having said extension thereon with an acetylnucleobase synthon to form an amide bond between said acetylnucleobase synthon and said secondary amine of said extension forming a new protected amine terminated resin bound peptide nucleic acid oligomer; e) deprotecting said protected amino group of said resin bound extended oligomer; and f) repeating steps a-e to further extend said oligomer; or g) terminating said synthesis.

Claim 29

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated structure on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said structure to form a resin bound structure having a monofunctional acetyl moiety thereon; c) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; d) treating said resin bound structure having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound structure having an extension thereon where said extension includes a secondary amine and a protected amino group; e) treating said structure having said extension thereon with an acetylnucleobase synthon to form an amide bond between said acetylnucleobase synthon and said secondary amine of said extension forming a new protected amine terminated resin bound peptide nucleic acid structure; f) deprotecting said protected amino group of said resin bound extended structure; and g) effecting one of terminating said procedure, step h) or step i); h) adding an amino acid monomeric unit to said deprotected amino group of said resin bound extended structure and repeating step g to further extend said structure; i) repeating steps b-f to further extend said structure.

Claim 30

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated structure on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said structure to form a resin bound structure having a monofunctional acetyl moiety thereon; c) selecting an alkyldiamine synthon having the first of its amino functional groups in the form of a protected amino group and the other of its amino functions groups as a free amine; d) treating said resin bound structure having said monofunctional acetyl moiety thereon with said alkyldiamine synthon to covalently bond said acetyl moiety and said free amine group of said alkyldiamine synthon forming a resin bound structure having an extension thereon where said extension includes a secondary amine and a protected amino group; e) treating said structure having said extension thereon with an acetylnucleobase synthon to form an amide bond between said acetylnucleobase synthon and said secondary amine of said extension forming a new protected amine terminated resin bound peptide nucleic acid structure; f) deprotecting said protected amino group of said resin bound extended structure; and g) effecting one of terminating said procedure, step h) or step i); h) adding an amino acid monomeric unit to said deprotected amino group of said resin bound extended structure and repeating step g to further extend said structure; i) repeating steps b-f to further extend said structure.

Claim 33

A method of adding further peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first functional group of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine-acetylnucleobase synthon wherein the first amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine-acetylnucleobase synthon to covalently bond said acetyl moiety and said secondary amide group of said alkyldiamine-acetylnucleobase synthon forming a resin bound extended oligomer having a protected amino group thereon; d) deprotecting said protected amino group of said resin bound extended oligomer to form a new amine terminated resin bound oligomer; and e) repeating steps a-d to further extend said oligomer or; f) terminating said synthesis.

Claim 34

A method of adding further peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first functional group of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine-acetylnucleobase synthon wherein the first amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine-acetylnucleobase synthon to covalently bond said acetyl moiety and said secondary amide group of said alkyldiamine-acetylnucleobase synthon forming a resin bound extended oligomer having a protected amino group thereon; d) deprotecting said protected amino group of said resin bound extended oligomer to form a new amine terminated resin bound oligomer; and e) repeating steps a-d to further extend said oligomer or; f) terminating said synthesis.

Claim 43

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound peptide nucleic acid oligomer having a monofunctional acetyl moiety thereon; b) selecting a plurality of alkyldiamine-acetylnucleobase synthons wherein in each such synthon the nucleobase is different from the nucleobase in others of said plurality of synthons and in each such synthon the first amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) treating said resin bound peptide nucleic acid oligomer having said monofunctional acetyl moiety thereon with said plurality of alkyldiamine-acetylnucleobase synthons to extend said peptide nucleic acid oligomer by the addition of a new protected amine terminated resin bound peptide nucleic acid unit; d) deprotecting said protected amino group of said resin bound peptide nucleic acid unit to extend resin bound peptide nucleic acid oligomer; and e) repeating steps a-d to further extend said oligomer; or f) terminating said synthesis.

Claim 44

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound peptide nucleic acid oligomer having a monofunctional acetyl moiety thereon; b) selecting a plurality of alkyldiamine-acetylnucleobase synthons wherein in each such synthon the nucleobase is different from the nucleobase in others of said plurality of synthons and in each such synthon the first amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) treating said resin bound peptide nucleic acid oligomer having said monofunctional acetyl moiety thereon with said plurality of alkyldiamine-acetylnucleobase synthons to extend said peptide nucleic acid oligomer by the addition of a new protected amine terminated resin bound peptide nucleic acid unit; d) deprotecting said protected amino group of said resin bound peptide nucleic acid unit to extend resin bound peptide nucleic acid oligomer; and e) repeating steps a-d to further extend said oligomer; or f) terminating said synthesis.

Claim 48

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said unit to form a resin bound peptide nucleic acid oligomer having a monofunctional acetyl moiety thereon; b) selecting a plurality of alkyldiamine-acetylnucleobase synthons wherein in each such synthon the nucleobase is different from the nucleobase in others of said plurality of synthons and in each such synthon the first of the amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) dividing said resin into portions; d) treating each of said portions of said resin bound peptide nucleic acid oligomer having said monofunctional acetyl moiety thereon with one of said plurality of alkyldiamine-acetylnucleobase synthons to extend said peptide nucleic acid oligomer by the addition of a protected amine terminated resin bound peptide nucleic acid unit; e) combining each of said portions of resin together; f) deprotecting said protected amino group of said resin bound peptide nucleic acid unit to extend said peptide nucleic acid oligomer; and g) repeating steps a-f to further extend said oligomer; or h) terminating said synthesis.

Claim 49

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first reactive site of said bifunctional acetyl synthon with said terminal amine of said unit to form a resin bound peptide nucleic acid oligomer having a monofunctional acetyl moiety thereon; b) selecting a plurality of alkyldiamine-acetylnucleobase synthons wherein in each such synthon the nucleobase is different from the nucleobase in others of said plurality of synthons and in each such synthon the first of the amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) dividing said resin into portions; d) treating each of said portions of said resin bound peptide nucleic acid oligomer having said monofunctional acetyl moiety thereon with one of said plurality of alkyldiamine-acetylnucleobase synthons to extend said peptide nucleic acid oligomer by the addition of a protected amine terminated resin bound peptide nucleic acid unit; e) combining each of said portions of resin together; f) deprotecting said protected amino group of said resin bound peptide nucleic acid unit to extend said peptide nucleic acid oligomer; and g) repeating steps a-f to further extend said oligomer; or h) terminating said synthesis.

Claim 53

A method of adding peptide nucleic acid units to one of an amine terminated peptide nucleic acid oligomer or an amine terminated amino acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first functional group of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine-acetylnucleobase synthon wherein the first of the amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine-acetylnucleobase synthon to covalently bond said acetyl moiety and said secondary amide group of said alkyldiamine-acetylnucleobase synthon forming a resin bound extended oligomer having a protected amino group thereon; d) deprotecting said protected amino group of said resin bound extended oligomer to form a new amine terminated resin bound oligomer; and e) repeating steps a-d to further extend said oligomer or; f) terminating said synthesis.

Claim 54

A method of adding peptide nucleic acid units to one of an amine terminated peptide nucleic acid oligomer or an amine terminated amino acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first functional group of said bifunctional acetyl synthon with said terminal amine of said oligomer to form a resin bound oligomer having a monofunctional acetyl moiety thereon; b) selecting an alkyldiamine-acetylnucleobase synthon wherein the first of the amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; c) treating said resin bound oligomer having said monofunctional acetyl moiety thereon with said alkyldiamine-acetylnucleobase synthon to covalently bond said acetyl moiety and said secondary amide group of said alkyldiamine-acetylnucleobase synthon forming a resin bound extended oligomer having a protected amino group thereon; d) deprotecting said protected amino group of said resin bound extended oligomer to form a new amine terminated resin bound oligomer; and e) repeating steps a-d to further extend said oligomer or; f) terminating said synthesis.

Claim 57

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated structure on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first functional group of said bifunctional acetyl synthon with said terminal amine of said structure to form a resin bound structure having a monofunctional acetyl moiety thereon; c) selecting an alkyldiamine-acetylnucleobase synthon wherein the first amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; d) treating said resin bound structure having said monofunctional acetyl moiety thereon with said alkyldiamine-acetylnucleobase synthon to covalently bond said acetyl moiety and said secondary amide group of said alkyldiamine-acetylnucleobase synthon forming a resin bound extended structure having a protected amino group thereon; e) deprotecting said protected amino group of said resin bound extended structure to form a new amine terminated resin bound structure; f) effecting one of terminating said procedure, step g) or step h); g) adding an amino acid monomeric unit to said deprotected amino group of said resin bound extended structure and repeating step g to further extend said structure; h) repeating steps b-e to further extend said structure.

Claim 58

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated structure on said solid phase synthesis resin with a bifunctional acetyl synthon to react a first functional group of said bifunctional acetyl synthon with said terminal amine of said structure to form a resin bound structure having a monofunctional acetyl moiety thereon; c) selecting an alkyldiamine-acetylnucleobase synthon wherein the first amine group of said synthon is present as a protected amino group and the other amine group of said synthon is incorporated into a secondary amide group with the acetylnucleobase portion of said synthon; d) treating said resin bound structure having said monofunctional acetyl moiety thereon with said alkyldiamine-acetylnucleobase synthon to covalently bond said acetyl moiety and said secondary amide group of said alkyldiamine-acetylnucleobase synthon forming a resin bound extended structure having a protected amino group thereon; e) deprotecting said protected amino group of said resin bound extended structure to form a new amine terminated resin bound structure; f) effecting one of terminating said procedure, step g) or step h); g) adding an amino acid monomeric unit to said deprotected amino group of said resin bound extended structure and repeating step g to further extend said structure; h) repeating steps b-e to further extend said structure.

Claim 61

A method of adding further peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a 1-(2-carbonylmethylnucleobase)-3-oxo-morpholine synthon to form a resin bound oligomer having a N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; b) treating said resin bound oligomer having said terminus moiety to convert said terminus moiety to an amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moiety thereby extending said oligomer by an amine terminated peptide nucleic acid unit; and c) repeating steps a and b to further extend said oligomer or; d) terminating said synthesis.

Claim 62

A method of adding further peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a 1-(2-carbonylmethylnucleobase)-3-oxo-morpholine synthon to form a resin bound oligomer having a N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; b) treating said resin bound oligomer having said terminus moiety to convert said terminus moiety to an amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moiety thereby extending said oligomer by an amine terminated peptide nucleic acid unit; and c) repeating steps a and b to further extend said oligomer or; d) terminating said synthesis.

Claim 65

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of 1-(2-carbonylmethyl-nucleobase)-3-oxo-morpholine synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) treating said amine terminated unit on said solid phase synthesis resin with said plurality of synthons forming resin bound oligomers having N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moieties thereon; c) treating said resin bound oligomers having said terminus moieties to convert said terminus moieties to amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moieties thereby extending said oligomers by one amine terminated peptide nucleic acid unit; d) repeating steps a-c to further extend said oligomer; or e) terminating said synthesis.

Claim 66

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of 1-(2-carbonylmethyl-nucleobase)-3-oxo-morpholine synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) treating said amine terminated unit on said solid phase synthesis resin with said plurality of synthons forming resin bound oligomers having N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moieties thereon; c) treating said resin bound oligomers having said terminus moieties to convert said terminus moieties to amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moieties thereby extending said oligomers by one amine terminated peptide nucleic acid unit; d) repeating steps a-c to further extend said oligomer; or e) terminating said synthesis.

Claim 68

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of 1-(2-carbonylmethyl-nucleobase)-3-oxo-morpholine synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) dividing said resin into portions; c) treating each of said portions of said amine terminated oligomer on said solid phase synthesis resin with one of said plurality of synthons forming resin bound oligomers having N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; d) combining all of said portions of resin together; e) treating said resin bound oligomers having said terminus moieties to convert said terminus moieties to amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moieties thereby extending said oligomers by one amine terminated peptide nucleic acid unit; f) repeating steps a-e to further extend said oligomer; or g) terminating said synthesis.

Claim 69

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of 1-(2-carbonylmethyl-nucleobase)-3-oxo-morpholine synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) dividing said resin into portions; c) treating each of said portions of said amine terminated oligomer on said solid phase synthesis resin with one of said plurality of synthons forming resin bound oligomers having N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; d) combining all of said portions of resin together; e) treating said resin bound oligomers having said terminus moieties to convert said terminus moieties to amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moieties thereby extending said oligomers by one amine terminated peptide nucleic acid unit; f) repeating steps a-e to further extend said oligomer; or g) terminating said synthesis.

Claim 71

A method of adding peptide nucleic acid units to one of an amine terminated peptide nucleic acid oligomer or an amine terminated amino acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a 1-(2-carbonylmethylnucleobase)-3-oxo-morpholine synthon forming a resin bound oligomer having a N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; b) treating said resin bound oligomer have said terminus moiety to convert said terminus moiety to an amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moiety; and c) repeating steps a and b to further extend said oligomer or; d) terminating said synthesis.

Claim 72

A method of adding peptide nucleic acid units to one of an amine terminated peptide nucleic acid oligomer or an amine terminated amino acid oligomer on a solid phase synthesis resin comprising the steps of: a) treating said amine terminated oligomer on said solid phase synthesis resin with a 1-(2-carbonylmethylnucleobase)-3-oxo-morpholine synthon forming a resin bound oligomer having a N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; b) treating said resin bound oligomer have said terminus moiety to convert said terminus moiety to an amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moiety; and c) repeating steps a and b to further extend said oligomer or; d) terminating said synthesis.

Claim 73

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated oligomer on said solid phase synthesis resin with a 1-(2-carbonylmethylnucleobase)-3-oxo-morpholine synthon forming a resin bound oligomer having a N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; c) treating said resin bound oligomer have said terminus moiety to convert said terminus moiety to an amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moiety; and d) effecting one of terminating said procedure, step e) or step f); e) adding an amino acid monomeric unit to said deprotected amino group of said resin bound extended structure and repeating step g to further extend said structure; f) repeating steps b and c to further extend said structure.

Claim 74

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated oligomer on said solid phase synthesis resin with a 1-(2-carbonylmethylnucleobase)-3-oxo-morpholine synthon forming a resin bound oligomer having a N-[2-(nucleobase)acetyl]-N-(hydroxyethyl)glycyl terminus moiety thereon; c) treating said resin bound oligomer have said terminus moiety to convert said terminus moiety to an amine terminated N-[2-(nucleobase)acetyl]-N-(aminoethyl)glycyl terminus moiety; and d) effecting one of terminating said procedure, step e) or step f); e) adding an amino acid monomeric unit to said deprotected amino group of said resin bound extended structure and repeating step g to further extend said structure; f) repeating steps b and c to further extend said structure.

Claim 75

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of peptide nucleic acid synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) treating said amine terminated unit on said solid phase synthesis resin with said plurality of synthons forming resin bound oligomers having random peptide nucleic acid terminus moieties thereon; c) repeating steps a and b to further extend said oligomer; or d) terminating said synthesis.

Claim 76

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of peptide nucleic acid synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) treating said amine terminated unit on said solid phase synthesis resin with said plurality of synthons forming resin bound oligomers having random peptide nucleic acid terminus moieties thereon; c) repeating steps a and b to further extend said oligomer; or d) terminating said synthesis.

Claim 79

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of peptide nucleic acid monomeric synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) dividing said resin into portions; c) treating each of said portions of said amine terminated oligomer on said solid phase synthesis resin with one of said plurality of synthons; d) combining all of said portions of resin together; e) repeating steps a-d to further extend said oligomer; or f) terminating said synthesis.

Claim 80

A method of adding further random peptide nucleic acid units to an amine terminated peptide nucleic acid oligomer on a solid phase synthesis resin comprising the steps of: a) selecting a plurality of peptide nucleic acid monomeric synthons wherein each of said synthons has a nucleobase that differs from the nucleobase of others of said synthons; b) dividing said resin into portions; c) treating each of said portions of said amine terminated oligomer on said solid phase synthesis resin with one of said plurality of synthons; d) combining all of said portions of resin together; e) repeating steps a-d to further extend said oligomer; or f) terminating said synthesis.

Claim 83

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated oligomer on said solid phase synthesis resin with a peptide nucleic acid monomeric synthon forming a resin bound structure having a terminus peptide nucleic acid moiety thereon; c) effecting one of terminating said procedure, step d) or step e); d) adding an amino acid monomeric unit to said resin bound structure to extended structure and repeating step c; e) repeating steps b and c to further extend said structure.

Claim 84

A method of preparing an oligomeric structure composed of mixed peptide nucleic acid units and amino acid units comprising the steps of: a) selecting one of an amine terminated peptide nucleic acid structure or an amine terminated amino acid structure on a solid phase synthesis resin and where said structure has at least one peptide nucleic acid unit or at least one amino acid unit; b) treating said amine terminated oligomer on said solid phase synthesis resin with a peptide nucleic acid monomeric synthon forming a resin bound structure having a terminus peptide nucleic acid moiety thereon; c) effecting one of terminating said procedure, step d) or step e); d) adding an amino acid monomeric unit to said resin bound structure to extended structure and repeating step c; e) repeating steps b and c to further extend said structure.