Thermodynamics of Nucleic Acid 鈥淪hape Readout鈥?by an Aminosugar

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• 作者：Hongjuan Xi ; Erik Davis ; Nihar Ranjan ; Liang Xue ; David Hyde-Volpe ; Dev P. Arya
• 刊名：Biochemistry
• 出版年：2011
• 出版时间：October 25, 2011
• 年：2011
• 卷：50
• 期：42
• 页码：9088-9113
• 全文大小：1407K
• 年卷期：v.50,no.42(October 25, 2011)
• ISSN：1520-4995

文摘

Recognition of nucleic acids is important for our understanding of nucleic acid structure as well as for our understanding of nucleic acid鈥損rotein interactions. In addition to the direct readout mechanisms of nucleic acids such as H-bonding, shape recognition of nucleic acids is being increasingly recognized as playing an equally important role in DNA recognition. Competition dialysis, UV, flourescent intercalator displacement (FID), computational docking, and calorimetry studies were conducted to study the interaction of neomycin with a variety of nucleic acid conformations (shapes). At pH 5.5, the results suggest the following. (1) Neomycin binds three RNA structures [16S A site rRNA, poly(rA)路poly(rA), and poly(rA)路poly(rU)] with high affinities (K_a 10p>7p> Mp>鈥?p>). (2) The binding of neomycin to A-form GC-rich oligomer d(A₂G₁₅C₁₅T₂)₂ has an affinity comparable to those of RNA structures. (3) The binding of neomycin to DNA路RNA hybrids shows a 3-fold variance that can be attributed to their structural differences [for poly(dA)路poly(rU), K_a = 9.4 脳 10p>6p> Mp>鈥?p>, and for poly(rA)路poly(dT), K_a = 3.1 脳 10p>6p> Mp>鈥?p>]. (4) The interaction of neomycin with DNA triplex poly(dA)路2poly(dT) yields a binding affinity (K_a) of 2.4 脳 10p>5p> Mp>鈥?p>. (5) Poly(dA-dT)₂ shows the lowest association constant for all nucleic acids studied (K_a < 10p>5p>). (6) Neomycin binds to G-quadruplexes with K_a values of 10p>4p>鈥?0p>5p> Mp>鈥?p>. (7) Computational studies show that the decrease in major groove width in the B to A transition correlates with increasing neomycin affinity. Neomycin鈥檚 affinity for various nucleic acid structures can be ranked as follows: RNAs and GC-rich d(A₂G₁₅C₁₅T₂)₂ structures > poly(dA)路poly(rU) > poly(rA)路poly(dT) > T路A-T triplex, G-quadruplex, B-form AT-rich, or GC-rich DNA sequences. The results illustrate the first example of a small molecule-based 鈥渟hape readout鈥?of different nucleic acid conformations.