Carbamate-derivatized nucleosides and oligonucleosides

Abstract

Nucleosides and oligonucleosides functionalized to include carbamate functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the carbamate group.

1 . A compound comprising a plurality of linked nucleosides, wherein: 
 each nucleoside includes a ribofuranosyl sugar portion and a base portion; and    at least one of said nucleosides bears at a 2′-O-position or a 3′-O-position a substituent having formula:      —RA-N—C(X)-O—R1a  or  —C(X)-N(R1b)(R1c)    where: 
 RA is alkyl having from 1 to about 10 carbon atoms or (CH2—CH2-Q) x ;  
 R1a is alkenyl having 2 to about 10 carbon atoms;  
 R1b and R1c, independently, are H, R2, RA, an amine protecting group or have formula RA-N(R1d)(R1e), C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R1d and R1e, independently, are H, R2, RA, an amine protecting group or have formula C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a reporter enzyme, a peptide, a protein, includes folic acid, or has formula -Q-(CH2CH2-Q-) x —R3;  
 X is O or S;  
 each Q is, independently, is NH, O, or S;  
 x is 1 to about 200;  
 R3 is H, RA, C(O)OH, C(O)ORA, C(O)R4, RA-N3, or RA-NH2;  
 R4 is Cl, Br, I, SO 2 R5 or has structure:  
                     
 m is 2 to 7; and  
 R5 alkyl having 1 to about 10 carbon atoms.  
   
     
     
         2 - 19 . (Cancelled)  
     
     
         20 . A nucleoside comprising a ribofuranosyl sugar portion and a base portion, wherein said nucleoside bears at a 2′-O-position or a 3′-O-position a substituent having formula:  
         —RA-N—C(X)-O—R1a  or  —C(X)-N(R1b)(R1c)  
       where: 
 RA is alkyl having from 1 to about 10 carbon atoms or (CH2-CH2-Q) x ;  
 R1a is alkenyl having 2 to about 10 carbon atoms;  
 R1b and R1c, independently, are H, R2, RA, an amine protecting group or have formula RA-N(R1d)(R1e), C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R1d and R1e, independently, are H, R2, RA, an amine protecting group or have formula C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a reporter enzyme, a peptide, a protein, includes folic acid, or has formula -Q-(CH2CH2-Q-) x —R3;  
 X is O or S;  
 each Q is, independently, is NH, O, or S;  
 x is 1 to about 200;  
 R3 is H, RA, C(O)OH, C(O)ORA, C(O)R4, RA-N3, or RA-NH2;  
 R4 is Cl, Br, I, SO 2 R5 or has structure:  
                     
 m is 2 to 7; and  
 R5 alkyl having 1 to about 10 carbon atoms.  
 
     
     
         21 . A compound comprising a plurality of linked nucleosides, wherein: 
 each nucleoside includes a ribofuranosyl sugar portion and a base portion; and    at least one of said nucleosides includes a pyrimidine base which bears at its 5-position a substituent having formula:      —RA-O—C(X)-N(R1b)(R1c)    where: 
 RA is alkyl having from 1 to about 10 carbon atoms or (CH2—CH2-Q)x;  
 R1b and R1c, independently, are H, R2, RA, an amine protecting group or have formula RA-N(R1d)(R1e), C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R1d and R1e, independently, are H, R2, RA, an amine protecting group or have formula C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a reporter enzyme, a peptide, a protein, includes folic acid, or has formula -Q-(CH2CH2-Q-) x —R3;  
 X is O or S;  
 each Q is, independently, is NH, O, or S;  
 x is 1 to about 200;  
 R3 is H, RA, C(O)OH, C(O)ORA, C(O)R4, RA-N3, or RA-NH2;  
 R4 is Cl, Br, I, SO 2 R5 or has structure:  
                     
 m is 2 to 7; and  
 R5 alkyl having 1 to about 10 carbon atoms.  
   
     
     
         22 . A nucleoside comprising a ribofuranosyl sugar portion and a pyrimiddine base portion, wherein said base portion bears at its 5-position a substituent having formula:  
         —RA-O—C(X)—N(R1b)(R1c)  where: 
 RA is alkyl having from 1 to about 10 carbon atoms or (CH2-CH2-Q)x;  
 R1b and R1c, independently, are H, R2, RA, an amine protecting group or have formula RA-N(R1d)(R1e), C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R1d and R1e, independently, are H, R2, RA, an amine protecting group or have formula C(X)-R2, C(X)-RA-R2, C(X)-Q-RA-R2, or C(X)-Q-R2;  
 R2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a reporter enzyme, a peptide, a protein, includes folic acid, or has formula -Q-(CH2CH2-Q-)x-R3;  
 X is O or S;  
 each Q is, independently, is NH, O, or S;  
 x is 1 to about 200;  
 R3 is H, RA, C(O)OH, C(O)ORA, C(O)R4, RA-N3, or RA-NH2;  
 R4 is Cl, Br, I, SO 2 R5 or has structure:  
                     
 m is 2 to 7; and  
 R5 alkyl having 1 to about 10 carbon atoms.  
   
     
     
         23 . (Cancelled).  
     
     
         24 . A method for modulating the production of a protein by an organism comprising contacting an organism with a compound of  claim 20 .  
     
     
         25 . (Cancelled).  
     
     
         26 . A method for modulating the production of a protein by an organism comprising contacting an organism with a compound of  claim 22 .  
     
     
         27 . (Cancelled).  
     
     
         28 . A method of treating an animal having a disease characterized by undesired production of protein comprising contacting said animal with a compound of claim  
     
     
         29 . (Cancelled).  
     
     
         30 . A method of treating an animal having a disease characterized by undesired production of protein comprising contacting said animal with a compound of  claim 22 .  
     
     
         31 . (Cancelled).  
     
     
         32 . A method for detecting the presence or absence of an RNA in a biological sample suspected of containing said RNA comprising contacting said sample with a compound of  claim 20 .  
     
     
         33 . (Cancelled).  
     
     
         34 . A method for detecting the presence or absence of an RNA in a biological sample suspected of containing said RNA comprising contacting said sample with a compound of  claim 22.