TY - JOUR
T1 - Pyrimidine motif triplexes containing polypurine RNA or DNA with oligo 2'-O-methyl or DNA triplex forming oligonucleotides
AU - Beban, Marc
AU - Miller, Paul S.
N1 - Funding Information:
The authors would like to thank Ms. Tomoko Hamma and Dr. David Noll for assistance in preparing this manuscript. This work was supported in part by a Grant from the National Institutes of Health, GM 57140.
PY - 2000/6/21
Y1 - 2000/6/21
N2 - Triplex forming oligonucleotides (TFOs) are potentially useful in targeting RNA for antisense therapeutic applications. To determine the feasibility of targeting polypurine RNA with nuclease-resistant oligonucleotides, TFOs containing 2'-deoxy or 2'-O-methyl (2'-OMe) backbones, designed to form pyrimidine motif triplexes with RNA, were synthesized. TFOs were made which can form trimolecular triplexes, or bimolecular, 'clamp' triplexes with polypurine RNA and DNA. It was found that the relative stabilities of the triplexes formed followed the order: M·DM(clamp)>>>D·DD˜M·DD>M·RM>D·DM>M·RD˜M·DM, where M is a 2'-OMe, D is a DNA and R is an RNA backbone. The third strand is listed first, separated by a dot from the purine strand of the Watson-Crick duplex, followed by the pyrimidine strand of the duplex. The results described here provide insight into the feasibility of using TFOs containing a 2'-OMe backbone as antisense agents.
AB - Triplex forming oligonucleotides (TFOs) are potentially useful in targeting RNA for antisense therapeutic applications. To determine the feasibility of targeting polypurine RNA with nuclease-resistant oligonucleotides, TFOs containing 2'-deoxy or 2'-O-methyl (2'-OMe) backbones, designed to form pyrimidine motif triplexes with RNA, were synthesized. TFOs were made which can form trimolecular triplexes, or bimolecular, 'clamp' triplexes with polypurine RNA and DNA. It was found that the relative stabilities of the triplexes formed followed the order: M·DM(clamp)>>>D·DD˜M·DD>M·RM>D·DM>M·RD˜M·DM, where M is a 2'-OMe, D is a DNA and R is an RNA backbone. The third strand is listed first, separated by a dot from the purine strand of the Watson-Crick duplex, followed by the pyrimidine strand of the duplex. The results described here provide insight into the feasibility of using TFOs containing a 2'-OMe backbone as antisense agents.
KW - 2'-O-Methyl
KW - Antisense
KW - RNA
KW - Triplex forming oligonucleotide
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U2 - 10.1016/S0167-4781(00)00107-X
DO - 10.1016/S0167-4781(00)00107-X
M3 - Article
C2 - 10858542
AN - SCOPUS:0034697798
SN - 0167-4781
VL - 1492
SP - 155
EP - 162
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
IS - 1
ER -