Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue improves the 3'-exonuclease stability of 2'-5'-oligoadenylate-antisense conjugates.
Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue at the 3'-terminus of DNA or 2-5A-DNA sequences resulted in a significantly enhanced 3'-exonuclease resistance while the affinity for complementary RNA was only slightly decreased. Furthermore, the binding to and activation of human RNase L by thus modified 2-5A-DNA conjugates was not altered as compared to the parent unmodified 2-5A-DNAs.
Verheijen
J C
JC
Leiden Institute of Chemistry, Gorlaeus Laboratories, The Netherlands.
van Roon
A M
AM
Meeuwenoord
N J
NJ
Stuivenberg
H R
HR
Bayly
S F
SF
Chen
L
L
van der Marel
G A
GA
Torrence
P F
PF
van Boom
J H
JH
D000227:Adenine Nucleotides / Q000737:chemistry*; D001483:Base Sequence; D016373:DNA, Antisense / Q000737:chemistry*; D004722:Endoribonucleases / Q000378:metabolism; D004789:Enzyme Activation; D005092:Exonucleases / Q000378:metabolism*; D006801:Humans; D009711:Nucleotides / Q000737:chemistry*; D009843:Oligoribonucleotides / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics
D000227:Adenine Nucleotides; D016373:DNA, Antisense; D009711:Nucleotides; D009843:Oligoribonucleotides; D012333:RNA, Messenger; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; D005092:Exonucleases; C022650:spleen exonuclease; C031956:2-5A-dependent ribonuclease