TRIPLEX FORMATION WITH A ANOMERS OF PURINE-RICH AND PYRIMIDINE-RICH OLIGODEOXYNUCLEOTIDES

被引:26
作者
NOONBERG, SB
FRANCOIS, JC
PRASEUTH, D
GUIEYSSEPEUGEOT, AL
LACOSTE, J
GARESTIER, T
HELENE, C
机构
[1] MUSEUM NATL HIST NAT, BIOPHYS LAB, CNRS, UA 481, INSERM, U201, F-75231 PARIS 05, FRANCE
[2] UNIV CALIF SAN FRANCISCO, CANC RES INST, SAN FRANCISCO, CA 94143 USA
关键词
D O I
10.1093/nar/23.20.4042
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclease-resistant alpha anomers of pyrimidine-rich CT-and purine-rich GA- and GT-containing oliganucleotides were investigated for their tripler-forming potential and compared with their corresponding nuclease-sensitive beta anomers. Both 23mer CT-alpha and 23mer CT-beta had quite similar tripler binding affinities. Synthetic 23mer GT-alpha oligonucleotides were capable of tripler formation with binding affinities slightly lower than corresponding 23mer GT-beta oligonucleotides, The orientation of third strand GT-alpha binding was parallel to the purine strand of the duplex DNA target, whereas the orientation of third strand GT-beta binding was found to be antiparallel. Tripler formation with both GT oligonucleotides showed the typical dependence on magnesium and temperature, In contrast, 23mer GA-alpha origonucleotides did not support tripler formation in either orientation under a variety of experimental conditions, whereas the corresponding 23mer GA-beta oligonucleotides demonstrated strong tripler formation in the antiparallel orientation. GA-alpha oligonucleotides covalently conjugated to acridine were similarly unable to demonstrate tripler formation. GA-alpha oligonucleotides, in contrast to GT-alpha oligonucleotides, were capable of self-association, detectable by gel retardation and UV spectroscopy, but competing self-association could not fully account for the lack of tripler formation. Thus for in vivo tripler gene regulation strategies using GT oligonucleotides the non-natural alpha anomer may be a feasible alternative to the natural beta anomer, allowing for a comparable degree of tripler formation without rapid cellular degradation, However, a anomeric inversion does not appear to be a feasible alternative in applications involving GA oligonucleotides.
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页码:4042 / 4049
页数:8
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