Enzymatic hydrolysis and biological activity of oligonucleotides containing 5-substituted pyrimidine bases.
Two series of alternating ODNs containing 5-n.alkyl-, alkenyl- and alkynyl-dU and -dC units have been prepared in order to study the kinetics of their hydrolysis by SV PDE and human serum, respectively. Both in (r5dUpdA)10 and (r5dCpdG)6 series the rate of hydrolysis decreased with increasing length of side-chain. Replacement of thymidines by 5-hexynyl-dU in different antisense oligomers resulted in considerably higher biological activity relative to that of the thymidine-containing counterparts.
Otvös
L
L
Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
Sági
J
J
Sági
G
G
Szemzõ
A
A
Tóth
F D
FD
Jeney
A
A
D001769:Blood; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011743:Pyrimidines / Q000737:chemistry*
D009841:Oligonucleotides; D011743:Pyrimidines; D010727:Phosphoric Diester Hydrolases