Methods of making conjugated 4' desmethyl nucleoside analog compounds

Claim 1

A method for forming a 4'-desmethyl conjugated monomer having structure: ##STR13## comprising the steps of: (a) providing a synthon having structure: ##STR14## and (b) contacting this synthon with an activated conjugating group; the contacting being for a time and under reaction conditions sufficient to form the conjugated monomer; wherein: R L is a group of formula: R.sub.C -- Y!.sub.C --Z-- R C is O-alkyl, O-alkenyl, O-alkynyl, a polyamine, a polyether, a steroid molecule, a reporter molecule, an aromatic lipophilic molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, a carbohydrate, a terpene molecule, a phospholipid, an intercalator, a cell receptor binding molecule, a crosslinking agent, of a porphyrin; Z is O, S or HN; Y is a bivalent linker; e is 0 or 1; B x is a nucleobase; X is H, OH, O-alkyl, O-alkoxylalkyl, O-alkylamino, or F; J is a leaving group; Q is O, S, CH 2 , CHF or CF 2 ; and R D is H, hydroxyl, an activated phosphorous group, a nucleoside, an activated nucleotide, a nucleotide, an oligonucleotide, an oligonucleoside or a protected derivative thereof.

Claim 2

A method for forming a 4'-desmethyl conjugated monomer having structure: ##STR13## comprising the steps of: (a) providing a synthon having structure: ##STR14## and (b) contacting this synthon with an activated conjugating group; the contacting being for a time and under reaction conditions sufficient to form the conjugated monomer; wherein: R L is a group of formula: R.sub.C -- Y!.sub.C --Z-- R C is O-alkyl, O-alkenyl, O-alkynyl, a polyamine, a polyether, a steroid molecule, a reporter molecule, an aromatic lipophilic molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, a carbohydrate, a terpene molecule, a phospholipid, an intercalator, a cell receptor binding molecule, a crosslinking agent, of a porphyrin; Z is O, S or HN; Y is a bivalent linker; e is 0 or 1; B x is a nucleobase; X is H, OH, O-alkyl, O-alkoxylalkyl, O-alkylamino, or F; J is a leaving group; Q is O, S, CH 2 , CHF or CF 2 ; and R D is H, hydroxyl, an activated phosphorous group, a nucleoside, an activated nucleotide, a nucleotide, an oligonucleotide, an oligonucleoside or a protected derivative thereof.

Claim 5

A method for forming a 4'-desmethyl conjugate oligomer having structure: ##STR15## comprising the steps of: (a) providing a first synthon having structure: ##STR16## and (b) contacting the first synthon with a second synthon having structure: ##STR17## the contacting being for a time and under reaction conditions sufficient to form the conjugated oligomer; wherein: R L is a group of formula: R.sub.C -- Y!.sub.e --Z-- R C is O-alkyl, O-alkynyl, a polyamine, a polyether, a steroid molecule, a reporter molecule, an aromatic lipophilic molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, a carbohydrate, a terpene molecule, a phospholipid, an intercalator, a cell receptor binding molecule, a crosslinking agent, or a porphyrin; Z is O, S or HN; Y is a bivalent linker; e is 0 or 1; E is a phosphodiester, phosphorothioate, phosphorodithioate, phosphamidate, alkyl phosphonate or phosphotriester phosphorous linking group; R E is an activated phosphorous group; W is H, a hydroxyl protecting group or a solid state support; k is an integer from 0 to 50; B x is a nucleobase; X is H, OH, O-alkyl, O-alkoxylalkyl, O-alkylamino, or F; and Q is O, S, CH 2 , CMF or CF 2 .

Claim 6

A method for forming a 4'-desmethyl conjugate oligomer having structure: ##STR15## comprising the steps of: (a) providing a first synthon having structure: ##STR16## and (b) contacting the first synthon with a second synthon having structure: ##STR17## the contacting being for a time and under reaction conditions sufficient to form the conjugated oligomer; wherein: R L is a group of formula: R.sub.C -- Y!.sub.e --Z-- R C is O-alkyl, O-alkynyl, a polyamine, a polyether, a steroid molecule, a reporter molecule, an aromatic lipophilic molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, a carbohydrate, a terpene molecule, a phospholipid, an intercalator, a cell receptor binding molecule, a crosslinking agent, or a porphyrin; Z is O, S or HN; Y is a bivalent linker; e is 0 or 1; E is a phosphodiester, phosphorothioate, phosphorodithioate, phosphamidate, alkyl phosphonate or phosphotriester phosphorous linking group; R E is an activated phosphorous group; W is H, a hydroxyl protecting group or a solid state support; k is an integer from 0 to 50; B x is a nucleobase; X is H, OH, O-alkyl, O-alkoxylalkyl, O-alkylamino, or F; and Q is O, S, CH 2 , CMF or CF 2 .

Claim 7

A method for forming an oligonucleotide having a conjugate group thereon comprising the steps (a) selecting an oligonucleotide having a 4'-desmethyl nucleoside at the 5'-terminal position of the oligonucleotide; and (b) linking a conjugate group to said 4'-desmethyl nucleoside, to form said oligonucleotide having said conjugate group thereon.

Claim 8

A method for forming an oligonucleotide having a conjugate group thereon comprising the steps (a) selecting an oligonucleotide having a 4'-desmethyl nucleoside at the 5'-terminal position of the oligonucleotide; and (b) linking a conjugate group to said 4'-desmethyl nucleoside, to form said oligonucleotide having said conjugate group thereon.