发夹微促性腺素在小沟中的DNA序列识别

DNA sequence recognition in the minor groove by hairpin microgonotropens.

作者信息

Kahane Alexandra L, Bruice Thomas C

机构信息

Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, CA 93106, USA.

出版信息

Bioorg Med Chem Lett. 2006 Dec 15;16(24):6255-61. doi: 10.1016/j.bmcl.2006.09.032. Epub 2006 Oct 10.

DOI:10.1016/j.bmcl.2006.09.032

PMID:17035007

Abstract

Two novel microgonotropens (MGTs) comprised of hairpin N-propylaminepyrrole polyamides linked to a Hoechst 33258 (Ht) analogue (3 and 4) were synthesized on solid phase by adopting an Fmoc technique using a series of HOBt mediated coupling reactions. The dsDNA-binding properties of MGTs 3 and 4 were determined by thermal denaturation experiments. Both MGTs were found to be selective for their nine-bp match dsDNA sequence 9 and were less tolerant of G/C bp substitutions in the binding region than linear progenitor MGT 1. MGT 3 was intolerant of a G/C substitution located in the middle of the binding region and did not bind to sequences 13 and 14. MGT 4 also did not bind to sequence 13, and its linker-bound Ht moiety was found to be more sensitive to a G/C substitution in the Ht-binding target, as demonstrated by the lack of binding to sequence 16.

摘要

通过采用Fmoc技术，利用一系列1-羟基苯并三唑（HOBt）介导的偶联反应，在固相上合成了两种新型的微促性腺激素（MGTs），它们由与Hoechst 33258（Ht）类似物相连的发夹型N-丙基胺吡咯聚酰胺组成（3和4）。通过热变性实验测定了MGTs 3和4与双链DNA（dsDNA）的结合特性。发现这两种MGTs对其九碱基对匹配的dsDNA序列9具有选择性，并且在结合区域中对G/C碱基对取代的耐受性低于线性亲本MGT 1。MGT 3对位于结合区域中间的G/C取代不耐受，并且不与序列13和14结合。MGT 4也不与序列13结合，并且发现其连接子连接的Ht部分对Ht结合靶标中的G/C取代更敏感，如不与序列16结合所示。