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Conformations of single-stranded DNA oligonucleotides and their actinomycin D complexes studied by high resolution proton NMR spectroscopy

Single-stranded (ss) DNA is important in regulating biological processes such as transcription due to its ability to form secondary structures. Four ss oligodeoxynucleotides (5'd$\lbrack$GTTAACCATAG$\rbrack$3', 5'd$\lbrack$GTAACCCATAG$\rbrack$3', 5'd$\lbrack$CTCGACGG$\rbrack$3', and 5'd$\lbrack$AACCCATT$\rbrack$3'), which bind to the anticancer drug actinomycin D, and assume folded conformations. The high resolution structure of 5'd$\lbrack$GTTAACCATAG$\rbrack$3' was determined by 2D $\sp1$H NMR and molecular modeling. The oligomer adopts an unusually stable hairpin structure. Its four-nucleotide hairpin loop possesses hydrophobic and hydrophilic faces. The hairpin stem consists of two Watson-Crick A:T base pairs, a G:T mismatch pair, and an unpaired 5'-terminal G. The conformational features of the loop as well as the GT mismatch and the 5'-terminal G of the stem are important in forming the stable hairpin and in actinomycin D recognition. / The first three oligonucleotides bind to actinomycin D with K$\rm \sb{a}$ = 10$\sp6\sim10\sp7$ M$\sp{-1}$. Actinomycin chromophore intercalates into double-stranded sites of secondary structures formed by the oligonucleotides. A guanine residue (G) is required for strong binding of actinomycin D to a single-stranded DNA. GT mismatches play an important role in enhancing binding terminator which induces dissociation of the RNA polymerase from the template. / Source: Dissertation Abstracts International, Volume: 56-11, Section: B, page: 6098. / Major Professor: Randolph L. Rill. / Thesis (Ph.D.)--The Florida State University, 1995.

Identiferoai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_77608
ContributorsSu, Lei., Florida State University
Source SetsFlorida State University
LanguageEnglish
Detected LanguageEnglish
TypeText
Format224 p.
RightsOn campus use only.
RelationDissertation Abstracts International

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