Means for sequential solid phase organic synthesis and methods using the same

Claim 2

A means for carrying out a sequential, solid phase organic synthesis to form a reaction product containing a plurality of reacted subunits comprising a foraminous container means having enclosed therein a known quantity of reactive particles, said particles being of a size that is larger than any of the foraminae defined by said container means and having a known amount of organic synthesis reactive functionality covalently linked to said particles, said reactive functionality being capable of reacting during said organic synthesis, said container means and said particles being substantially insoluble in water and in organic solvents.

Claim 3

The synthesis means according to claim 1 wherein said foraminous container means comprises polypropylene mesh.

Claim 4

The synthesis means according to claim 1 wherein said reactive functionality of said particles is a benzyl moiety that is a portion of a polymerized resin that constitutes substantially all of each of said particles, and the resin of said particles is comprised primarily of polymerized styrene cross-linked with divinyl benzene and includes a known amount of polymerized vinyl benzyl moiety, said polymerized vinyl benzyl moiety constituting said reactive benzyl moiety and providing a functional group through which said subunits may be covalently linked to said particles.

Claim 5

The synthesis means according to claim 1, including a plurality of said foraminous container means each having enclosed therein said known quantity of said reactive particles, said plurality of container means being integrally formed with each other.

Claim 6

A means for carrying out a solid phase organic synthesis to form a reaction product containing a plurality of reacted subunits comprising a foraminous container having enclosed therein a known quantity of solid support particles, said particles being of a size that is larger than any of the foraminae defined by said container and being linked to a known amount of identical organic synthesis subunits by selectively severable covalent bonds, each of said subunits containing a functional group capable of reacting during said organic synthesis, but that is protected from so reacting by a selectively removable covalently linked protecting group, said container and said particles being substantially insoluble in water and organic solvents and being non-reactive with hydrogen fluoride.

Claim 7

A means for carrying out a solid phase organic synthesis to form a reaction product containing a plurality of reacted subunits comprising a foraminous container having enclosed therein a known quantity of solid support particles, said particles being of a size that is larger than any of the foraminae defined by said container and being linked to a known amount of identical organic synthesis subunits by selectively severable covalent bonds, each of said subunits containing a functional group capable of reacting during said organic synthesis, but that is protected from so reacting by a selectively removable covalently linked protecting group, said container and said particles being substantially insoluble in water and organic solvents and being non-reactive with hydrogen fluoride.

Claim 8

The synthesis means according to claim 5 wherein said particles are hydrophobic resin beads comprised primarily of polymerized styrene cross-linked with divinyl benzene and include a known amount of polymerized vinyl benzene moiety through which said subunits are covalently linked to said beads, and said subunits are selected from the group consisting of (i) an alpha amino group-protected amino acid residue and (ii) an alpha amino group-protected and reactive side chain-protected amino acid residue.

Claim 9

A method of carrying out an organic solid phase synthesis to form a reaction product containing a plurality of desired reacted subunits comprising _the steps of: (a) providing a solid phase organic synthesis means of claim 1; (b) reacting first subunits with said reactive functionalities to form a selectively severable covalent bond between said first subunits and said particles, and to form a synthesis means containing particle-linked subunits, said first subunits including a first functional group that reacts with said reactive functionality and a second reactive functional group capable of reacting during said reaction, but that is protected from reaction by a selectively removable, covalently linked protecting group; (c) removing said protecting group from said second reactive functional group to form a synthesis means containing particle-linked subunits having free reactive functional groups; (d) admixing with the synthesis means containing particle-linked subunits having free reactive functional groups an excess of identical, known other subunits that contain (i) a functional group capable of reacting with the free reactive groups of said particle-linked subunits and (ii) a second reactive functional group capable of reacting during the organic synthesis, but that is protected from so reacting by a selectively removable covalently linked protecting group; (e) reacting said free reactive groups and said admixed functional groups to form covalent bonds, couple the subunit to the particle and form particle-linked subunit reaction products; (f) separating unreacted subunits from said particle-linked reaction products; (g) removing the protecting groups of the coupled subunits of step (d) to form particle-linked reaction products containing free reactive functional groups; (h) thereafter, serially repeating steps (d), (e), (f) and (g) until particle-linked reaction products containing the desired numer and identity of reacted subunits are synthesized; (i) severing said selectively severable bond between said first subunit and said particle to form a mixture of severed, free reaction products and reacted particles; (j) separating said severed, free reaction products from said reacted particles; and (k) recovering said severed reaction products.

Claim 14

The method according to claim 9 wherein said linked subunits are amino acid residues polypeptide bonded in a reaction product sequence.

Claim 15

The method according to claim 10 wherein said amino acid residue reaction product sequences correspond to the amino acid sequence of a single proteinaceous material except for the identity of one amino acid residue in each of said subunit reaction product sequences.

Claim 16

The method according to claim 9 further including serially repeating steps (c), (d) and (e) prior to step (f) until an admixture of synthesis means is formed in which each of said synthesis means contains a particle-linked subunit reaction product having a desired number and identity of reacted subunits.

Claim 17

The method according to claim 9 wherein a portion of the synthesis means of the synthesis means admixture of step (a) is enclosed in a resealingly closable, foraminous envelope means, said envelope means comprising first and second opposing webs at least one of which is foraminous, said webs being partially secured together at their peripheries; said first web being operably connected to a male portion of a resealable closure means, and said second web being operably connected to a female portion of said closure means whereby said closure means defines a mouth which communicates with the interior of said envelope means, said male and female portions of said closure means matingly engaging to resealably close said envelope means when pressed together in face-to-face relation, the foraminae of said envelope means being sized to permit drainage of a solvent used in said synthesis within a time period of at least 5 minutes at the synthesis temperature while retaining said synthesis means within said envelope means, said envelope means being substantially insoluble in water and organic solvents.