Recognition of a 10 base pair sequence of DNA and stereochemical control of the binding affinity of chiral hairpin polyamide-Hoechst 33258 conjugates

被引：11

作者：

Reddy, PM ^{[1
]}

Toporowski, JW ^{[1
]}

Kahane, AL ^{[1
]}

Bruice, TC ^{[1
]}

机构：

[1] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 24期

关键词：

chiral hairpin polyamide-Hoechst 33258 conjugates;

D O I：

10.1016/j.bmcl.2005.08.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Chiral hairpin polyamides linked to a Hoechst 33258 analogue at the alpha-position of the hairpin turn amino acid (1,2) were synthesized on solid phase by adopting Fmoc and ivDde techniques. The DNA-binding properties of enantiomeric conjugates I and 2, and N-terminal linked conjugate 3 for 8-14 bp sequences were determined by spectrofluorometric and thermal melting studies. Conjugates I and 2 recognize a 10 bp sequence, while conjugate 3 recognizes a 9 bp sequence. Interestingly, R-enantiomer I exhibited 10- to 30-fold higher binding affinities than S-enantiomer 2 for the DNA sequences studied. These binding differences were accounted for by molecular modeling studies, which revealed that the amide proton nearest to the chiral center in R-conjugate I is better positioned to form hydrogen bonds to the DNA bases, while S-conjugate 2 does not. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：5531 / 5536

页数：6

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