Thiol-derivatized nucleosides

Claim 2

A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nucleoside bears at a 2'-O-position, a 3'-O-position, or a 5'O-position a substituent having formula: --R.sub.s --S--R.sub.1 where: R S has formula R A , R A --C(O)--Q--R A RA--Q--R A --Q--R A ; each R A is independently selected from alkyl having from 1 to about 10 carbon atoms; each Q is independently selected from NH, O, and S; R 1 is H or a thiol protecting group or has formula S--R 2 , CH 2 C(O)--NH--R 2 , --CH 2 --CH═CH--C(O)--R 2 , --CH 2 --CH 2 --NH--S(O) 2 R 2 ; or (maleimido)--R 2; and R 2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a peptide, a protein, an alkylator, an intercalator, a crown ether, a crown amine, a porphyrin, a peptide nucleic acid, or a thiol attached to a poly(ethylene glycol).

Claim 3

The compound of claim 1 wherein R A is (CH 2 ) n where n is an integer from 1 to about 10.

Claim 4

The compound of claim 2 wherein n is 6.

Claim 5

The compound of claim 1 wherein R 1 is H or trityl.

Claim 6

The compound of claim 1 wherein R 1 is S--R 2 and R 2 is thiocholesterol.

Claim 7

The compound of claim 9 wherein R 1 is CH 2 C(O)--NH--R 2 and R 2 is o-phenanthroline.

Claim 8

The compound of claim 1 wherein R 1 is phospholipid maleimido, fluorescein maleimido, or pyrene maleimido.

Claim 9

The nucleoside of claim 1 wherein R 2 is a reporter group.

Claim 10

The nucleoside of claim 1 wherein R 2 is a reporter enzyme.

Claim 11

The nucleoside of claim 1 wherein R 2 is a cell receptor binding molecule.

Claim 12

A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nucleoside bears at a 2'-O-position, a 3'-O-position, or a 5'-O-position a substituent having formula: --R.sub.S --S--R.sub.1 where: R S has formula R A , R A --C(O)--Q--R A , R A --Q --R A --R A ; each R A is independently selected from alkyl having from 1 to about 10 carbon atoms; each Q is independently selected from NH, O, and S; R 1 is H or a thiol protecting group or has formula S--R 2 , CH 2 C(O)--NH--R 2 , CH 2 --CH═CH--C(O)--R 2 , --CH 2 --CH2--NH--S(O) 2 --R 2 , or (maleimido)--R 2 ; and R 2 is a crosslinking agent.

Claim 13

A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nucleoside bears at a 2'-O-position, a 3'-O-position, or a 5'-O-position a substituent having formula: --R.sub.S --S--R.sub.1 where: R S has formula R A , R A --C(O)--Q--R A , R A --Q --R A --R A ; each R A is independently selected from alkyl having from 1 to about 10 carbon atoms; each Q is independently selected from NH, O, and S; R 1 is H or a thiol protecting group or has formula S--R 2 , CH 2 C(O)--NH--R 2 , CH 2 --CH═CH--C(O)--R 2 , --CH 2 --CH2--NH--S(O) 2 --R 2 , or (maleimido)--R 2 ; and R 2 is a crosslinking agent.

Claim 14

A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nucleoside bears at a 5pyrimidine position or at a 2-, 6-, or 8-purine position a substituent having formula: --Q --R.sub.A --S--R.sub.1 ; or --C.tbd.C--R.sub.A --Q--C(0)--R.sub.A --S--R.sub.1 ; --CH═CH--C(O)--Q --R.sub.A --S--R.sub.1 ; or --CH═CH--R.sub.A --Q--C(O)--Q--R.sub.A --S--R.sub.1 ; where: each R A is independently alkyl having from 1 to about 10 carbon atoms; Q is NH, O, or S; R 1 is H or a thiol protecting group or has formula S--R 2 , CH 2 C(O)--NH--R 2 , CH 2 --CH═CH--C(O)--R 2 , --CH 2 --CH 2 --NH --S(O) 2 R 2 , or (maleimido)--R 2 ; and R 2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a peptide, a protein, an alkylator, an intercalator, a crown ether, a crown amine, a porphyrin, a peptide mucleic acid, or a thiol attached to a poly(ethylene glycol); provided that a 6-purine substituent does not have formula --NH--R A --S--R 1 when R 1 is H or a thiol protecting group.

Claim 15

A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nucleoside bears at a 5pyrimidine position or at a 2-, 6-, or 8-purine position a substituent having formula: --Q --R.sub.A --S--R.sub.1 ; or --C.tbd.C--R.sub.A --Q--C(0)--R.sub.A --S--R.sub.1 ; --CH═CH--C(O)--Q --R.sub.A --S--R.sub.1 ; or --CH═CH--R.sub.A --Q--C(O)--Q--R.sub.A --S--R.sub.1 ; where: each R A is independently alkyl having from 1 to about 10 carbon atoms; Q is NH, O, or S; R 1 is H or a thiol protecting group or has formula S--R 2 , CH 2 C(O)--NH--R 2 , CH 2 --CH═CH--C(O)--R 2 , --CH 2 --CH 2 --NH --S(O) 2 R 2 , or (maleimido)--R 2 ; and R 2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a peptide, a protein, an alkylator, an intercalator, a crown ether, a crown amine, a porphyrin, a peptide mucleic acid, or a thiol attached to a poly(ethylene glycol); provided that a 6-purine substituent does not have formula --NH--R A --S--R 1 when R 1 is H or a thiol protecting group.

Claim 16

The compound of claim 12 wherein R A is (CH 2 ) n where n is an integer from 1 to 10.

Claim 17

The compound of claim 13 wherein n is 6.

Claim 18

The compound of claim 12 wherein R 1 is H or trityl.

Claim 19

The compound of claim 13 wherein said nucleoside bears at a 5-pyrimidine position a substituent having formula --C.tbd.C--CH.sub.2 --NH--C(O)--(CH.sub.2).sub.n --S--R.sub.1.

Claim 20

The compound of claim 13 wherein said nucleoside bears at a 5-pyrimidine position a substituent having formula --CH═CH--C(O)--NH--(CH 2 ) n --S--R 1 .

Claim 21

The compound of claim 13 wherein said nucleoside bears at a 2- or 8-purine position a substituent having formula --NH--(CH 2 ) n --S--R 1 .

Claim 22

The compound of claim 13 wherein said nucleoside bears at a 2-, 6-, or 8-purine position a substituent having formula --S--(CH 2 ) n --S--R 1 .

Claim 23

The nucleoside of claim 12 wherein R 2 is a reporter group.

Claim 24

The nucleoside of claim 12 wherein R 2 is a reporter enzyme.

Claim 25

The nucleoside of claim 12 wherein R 2 s a cell receptor binding molecule.

Claim 26

A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nuceloside bears at a 5-pyrimidine positon or at a 2-, 6-, or 8-purine position a substitutent having formula: --Q--R.sub.A --S--R.sub.1 ; or --C.tbd.C--R.sub.A --Q--C(O)--R.sub.A --S--R.sub.1 ; --CH═Ch--C(O)--Q--R.sub.A --S--R.sub.1 ; or --CH═CH--R.sub.A --Q--C(O)--Q--R.sub.A --S--R.sub.1 ; wherein: each R A is independently alkyl having from 1 to about 10 carbon atoms; Q is NH, O, or S; R 1 is H or a thiol protecting group or has formula S--R 2 , CH 2 C(O)--NH--R 2 , CH 2 --CH═CH--C(O)--R 2 , --CH 2 --CH 2 --NH--S(O)-- 2 --R 2 , or (maleimido)--R 2 ; and R 2 is a crosslinking agent; provided that a 6-purine substituent does not have formula --NH--R A --S--R 1 when R 1 is H or a thiol protecting group.

Claim 27

A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nuceloside bears at a 5-pyrimidine positon or at a 2-, 6-, or 8-purine position a substitutent having formula: --Q--R.sub.A --S--R.sub.1 ; or --C.tbd.C--R.sub.A --Q--C(O)--R.sub.A --S--R.sub.1 ; --CH═Ch--C(O)--Q--R.sub.A --S--R.sub.1 ; or --CH═CH--R.sub.A --Q--C(O)--Q--R.sub.A --S--R.sub.1 ; wherein: each R A is independently alkyl having from 1 to about 10 carbon atoms; Q is NH, O, or S; R 1 is H or a thiol protecting group or has formula S--R 2 , CH 2 C(O)--NH--R 2 , CH 2 --CH═CH--C(O)--R 2 , --CH 2 --CH 2 --NH--S(O)-- 2 --R 2 , or (maleimido)--R 2 ; and R 2 is a crosslinking agent; provided that a 6-purine substituent does not have formula --NH--R A --S--R 1 when R 1 is H or a thiol protecting group.

Claim 28

A process for derivatizing a nucleoside bearing a 2'-hydroxy group, a 3'-hydroxy group, or a 5'-hydroxy group, comprising contacting said nucleoside with a compound having formula L 1 --R A --S--R 1a for a time and under conditions effective to form a linkage having formula --O--R A --S--R 1a , wherein L 1 is a leaving group and R 1a is an acid labile thiol protecting group.

Claim 29

A process for derivatizing a nucleoside bearing a 2'-hydroxy group, a 3'-hydroxy group, or a 5'-hydroxy group, comprising contacting said nucleoside with a compound having formula L 1 --R A --S--R 1a for a time and under conditions effective to form a linkage having formula --O--R A --S--R 1a , wherein L 1 is a leaving group and R 1a is an acid labile thiol protecting group.

Claim 30

The process of claim 24 further comprising contacting said linkage with acid to remove said protecting group.