Substituted purines and oligonucleotide cross-linking

A compound having the formula:

• ##STR27## wherein:
• G is N;
• X is NHR.sub.2 Q.sub.1 or OR.sub.2 Q.sub.1, wherein said R.sub.2 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.1 comprises a reactive or non-reactive functionality;
• Y is halogen, NH.sub.2, H, R.sub.3 Q.sub.2, or NHR.sub.3 Q.sub.2, wherein said R.sub.3 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.2 comprises a reactive or non-reactive functionality;
• W is R.sub.4 Q.sub.3, or NHR.sub.4 Q.sub.3, wherein said R.sub.4 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.3 comprises a reactive or non-reactive functionality;
• Z is H, a nitrogen protecting group, or a nucleoside sugar moiety;
• said reactive functionality is selected from the group consisting of halogens, heterocycles, heterocycloalkyls, heterocycloalkylamines, polyalkylamines, aminoalkylamines, ethers, esters, aldehydes, ketones, aryl groups, hydrazines, hydroxylamines, semicarbazides, thiosemicarbazides, hydrazones, hydrazides, alcohols, and thiols;
• and
• said unreactive functionality is selected from the group consisting of alkyl groups, polyamides, intercalators, and ethylene glycols.

A compound having the formula:

• ##STR28## wherein:
• G is N;
• X is halogen, NH.sub.2, OH, NHR.sub.2 Q.sub.1 or OR.sub.2 Q.sub.1, wherein said R.sub.2 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.1 comprises a reactive or non-reactive functionality;
• Y is R.sub.3 Q.sub.2, or NHR.sub.3 Q.sub.2, wherein said R.sub.3 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.2 comprises a reactive or non-reactive functionality;
• W is R.sub.4 Q.sub.3, or NHR.sub.4 Q.sub.3, wherein said R.sub.4 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.3 comprises a reactive or non-reactive functionality;
• Z is H, a nitrogen protecting group, or a nucleoside sugar moiety;
• said reactive functionality is selected from the group consisting of halogens, heterocycles, heterocycloalkyls, heterocycloalkylamines, polyalkylamines, aminoalkylamines, ethers, esters, aldehydes, ketches, aryl groups, hydrazines, hydroxylamines, semicarbazides, thiosemicarbazides, hydrazones, hydrazides, alcohols, and thiols;
• and
• said unreactive functionality is selected from the group consisting of alkyl groups, polyamides, intercalators, and ethylene glycols.

A compound having the formula:

• ##STR29## wherein:
• G is N;
• X is OR.sub.2 Q.sub.1, wherein said R.sub.2 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.1 comprises a reactive or non-reactive functionality;
• Y is halogen, H, R.sub.3 Q.sub.2, or NHR.sub.3 Q.sub.2, wherein said R.sub.3 is a hydrocarbyl group having from I to about 20 carbon atoms, and Q.sub.2 comprises a reactive or non-reactive functionality;
• W is H;
• Z is H, a nitrogen protecting group, or a nucleoside sugar moiety, provided that where Y is NHR.sub.3 Q.sub.2, said nucleoside sugar moiety is not a 2'-fluoro arabinofuranosyl sugar moiety;
• said reactive functionality is selected from the group consisting of halogens, heterocycles, heterocycloalkyls, heterocycloalkylamines, polyalkylamines, aminoalkylamines, ethers, esters, aldehydes, ketones, aryl groups, hydrazines, hydroxylamines, semicarbazides, thiosemicarbazides, hydrazones, hydrazides, alcohols, and thiols;
• and
• said unreactive functionality is selected from the group consisting of alkyl groups, polyamides, intercalators, and ethylene glycols.

A compound having the formula:

• ##STR30## wherein:
• G is N;
• X is NHR.sub.2 Q.sub.1 wherein said R.sub.2 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.1 comprises a reactive or non-reactive functionality;
• Y is R.sub.3 Q.sub.2, or NHR.sub.3 Q.sub.2, wherein said R.sub.3 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.2 comprises a reactive or non-reactive functionality;
• W is H;
• Z is H, a nitrogen protecting group, or a nucleoside sugar moiety, provided that where X is NHR.sub.2 Q.sub.1 and Y is NHR.sub.3 Q.sub.2, said nucleoside sugar moiety is not a 2'-fluoro arabinofuranosyl sugar moiety;
• said reactive functionality is selected from the group consisting of halogens, heterocycles, heterocycloalkyls, heterocycloalkylamines, polyalkylamines, aminoalkylamines, ethers, esters, aldehydes, ketones, hydrazines, hydroxylamines, semicarbazides, thiosemicarbazides, hydrazones, hydrazides, alcohols, and thiols;
• and
• said unreactive functionality is selected from the group consisting of alkyl groups, polyamides, intercalators and ethylene glycols.

An oligonucleotide having at least one nucleotide of the formula:

• ##STR31## wherein:
• G is CR.sub.1 or N;
• R.sub.z is H or a hydrocarbyl group having from 1 to 6 carbon atoms;
• X is halogen, NH.sub.2, OH, NHR.sub.2 Q.sub.1 or OR.sub.2 Q.sub.1, wherein said R.sub.2 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.1 comprises a reactive or non-reactive functionality;
• Y is halogen, NH.sub.2, H, R.sub.3 Q.sub.2, or NHR.sub.3 Q.sub.2, wherein said R.sub.3 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.2 comprises a reactive or non-reactive functionality;
• W is H, R.sub.4 Q.sub.3, or NHR.sub.4 Q.sub.3, wherein said R.sub.4 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.3 comprises a reactive or non-reactive functionality;
• Z is a nucleoside sugar moiety;
• said reactive functionality is selected from the group consisting of halogens, heterocycles, heterocycloalkyls, heterocycloalkylamines, polyalkylamines, aminoalkylamines, ethers, esters, aldehydes, ketones, aryl groups, hydrazines, hydroxylamines, semicarbazides, thiosemicarbazides, hydrazones, hydrazides, alcohols, and thiols;
• said unreactive functionality is selected from the group consisting of alkyl groups, polyamides, intercalators, and ethylene glycols;
• and
• wherein at least one of X, Y and W is selected such that X is NHR.sub.2 Q.sub.1 or OR.sub.2 Q.sub.1, Y is R.sub.3 Q.sub.2 or NHR.sub.3 Q.sub.2, or W is NHR.sub.4 Q.sub.3.

An oligonucleotide for affecting RNase H cleavage of RNA comprising:

• a first oligonucleotide region and a second oligonucleotide region;
• together said first and said second region having a nucleotide sequence essentially complementary to at least a portion of said RNA;
• said first region including at least one compound of the formula:
• ##STR32## wherein:
• G is CR.sub.1 or N;
• R.sub.1 is H or a hydrocarbyl group having from 1 to 6 carbon atoms;
• X is halogen, NH.sub.2, OH, NHR.sub.2 Q.sub.1 or OR.sub.2 Q.sub.1, wherein said R.sub.2 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.1 comprises a reactive or non-reactive functionality;
• Y is halogen, NH.sub.2, H, R.sub.3 Q.sub.2, or NHR.sub.3 Q.sub.2, wherein said R.sub.3 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.2 comprises a reactive or non-reactive functionality;
• w is H, R.sub.4 Q.sub.3, or NHR.sub.4 Q.sub.3, wherein said R.sub.4 is a hydrocarbyl group having from 1 to about 20 carbon atoms, and Q.sub.3 comprises a reactive or non-reactive functionality;
• Z is H, a nitrogen protecting group, or a nucleoside sugar moiety;
• said reactive functionality is selected from the group consisting of halogens, heterocycles, heterocycloalkyls, heterocycloalkylamines, polyalkylamines, aminoalkylamines, ethers, esters, aldehydes, ketones, aryl groups, hydrazines, hydroxylamines, semicarbazides, thiosemicarbazides, hydrazonezides, alcozides, alcohols, and thiols;
• said unreactive functionality is selected from the group consisting of alkyl groups, polyamides, intercalators, and ethylene glycols;
• wherein at least one of X, Y and W is selected such that X is NHR.sub.2 Q.sub.1 or OR.sub.2 Q.sub.1, Y is R.sub.3 Q.sub.2 or NHR.sub.3 Q.sub.a, or W is NHR.sub.4 Q.sub.3 ;
• and
• said second region including a plurality of consecutive phosphorothioate linked nucleotides having a 2'-deoxy-erythropentofuranosyl sugar moiety.

A cross-linked nucleic acid comprising:

• a first oligonucleotide region and a second oligonucleotide region, wherein said first region includes at least one nucleotide of the formula:
• ##STR33## wherein:
• G is CR.sub.5 or N;
• R.sub.5 is H or a hydrocarbyl group having from 1 to 6 carbon atoms;
• X is halogen NH.sub.2, OH, NHR.sub.6 Q.sub.1, OR.sub.6 Q.sub.1, NHJ, OJ or SJ wherein said R.sub.6 is H or a hydrocarbyl group having from 2 to about 20 carbon atoms;
• Q.sub.1 comprises at least one reactive or non-reactive functionality;
• J comprises a space spanning group R.sub.7 and an active functional group Q.sub.4 ;
• Y is halogen, NH.sub.2, H, SH, OH, NHJ, OJ or SJ where J comprises a space spanning group R.sub.7 and an active functional group Q.sub.4 ;
• W is H, NHK, OK or SK where K comprises a space spanning group R.sub.7 and an active non-psoralen functional group Q.sub.5 ;
• Z is H, a nitrogen protecting group, or a sugar moiety;
• said space spanning group R.sub.7 is a hydrocarbyl group having from 2 to about 20 carbon atoms;
• at least one of said X or Y groups is NHJ, OJ or SJ, or at least one of said W groups is NHK, OK or SK;
• and
• said second region includes a second nucleotide of said formula capable of covalently bonding with said J group or said W group of said nucleotide of said formula in said first oligonucleotide region thereby forming a covalent cross-linkage between said first and said second oligonucleotide regions.