PMID: 9443977Mar 14, 1998Paper

Solution structure of a highly stable DNA duplex conjugated to a minor groove binder

Nucleic Acids Research
S KumarB I Schweitzer

Abstract

The tripeptide 1,2-dihydro-(3 H )-pyrrolo[3,2- e ]indole-7-carboxylate (CDPI3) binds to the minor groove of DNA with high affinity. When this minor groove binder is conjugated to the 5'-end of short oligonucleotides the conjugates form unusually stable hybrids with complementary DNA and thus may have useful diagnostic and/or therapeutic applications. In order to gain an understanding of the structural interactions between the CDPI3minor groove binding moiety and the DNA, we have determined and compared the solution structure of a duplex consisting of oligodeoxyribonucleotide 5'-TGATTATCTG-3' conjugated at the 5'-end to CDPI3 and its complementary strand to an unmodified control duplex of the same sequence using nuclear magnetic resonance techniques. Thermal denaturation studies indicated that the hybrid of this conjugate with its complementary strand had a melting temperature that was 30 degrees C higher compared with the unmodified control duplex. Following restrained molecular dynamics and relaxation matrix refinement, the solution structure of the CDPI3-conjugated DNA duplex demonstrated that the overall shape of the duplex was that of a straight B-type helix and that the CDPI3moiety was bound snugly in the minor groove, whe...Continue Reading

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Citations

Mar 21, 2003·Biochemical and Biophysical Research Communications·M Hadi Zareie, Philip B Lukins
Jun 17, 2016·Nucleic Acids Research·Rui WangJia Sheng
Apr 23, 2008·Current Protocols in Nucleic Acid Chemistry·Igor KutyavinMichael W Reed
Oct 10, 2018·ACS Applied Materials & Interfaces·Indu TripathiDipanjan Pan

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