Synthesis and DNA-binding properties of 1,2,3-triazole-linked H-pin pyrrole- and imidazole-containing polyamides formed by the Huisgen reaction

Heterocyclic communications

article

Balaji Babu¹  Samuel Tzou¹  Olivia Sweat¹  Toni Rice¹  Hilary Mackay¹  Michael D. Seymour¹  Moses Lee¹  Kimberly A. Brien¹  Vijay Satam¹  Adam Plaunt¹  Mary Pressler¹  Hao Shen¹  Shannon Alger¹  Ross Ogilvie¹  Robert Sjoholm¹ 

[1] Department of Chemistry, Division of Natural and Applied Sciences, Hope College

关键词: DNA;    imidazoles;    polyamides;    pyrroles;    sequence specificity;    1;    2;    3-triazole;   

DOI  :  10.1515/hc-2012-0003

学科分类：内科医学

来源: De Gruyter

【 摘 要 】

Covalently linked pyrrole (Py)- and imidazole (Im)-containing H-pin polyamides bind in the minor groove of specific DNA sequences with high affinity. The synthesis of 1,2,3-triazole-linked and heterodimeric H-pin polyamides 13a , b formed from the Huisgen reaction of an alkyne-containing f-PyPyPy ( 6 ) with an azide-containing f-ImPyIm ( 7 ) is reported. The reaction proceeded smoothly under thermal conditions to give an inseparable mixture of 1,4- and 1,5-isomers ( 13a and 13b , respectively) by column chromatography. When the reaction was conducted under ‘click’ or Cu(I)-catalyzed conditions or in the presence of the cognate DNA sequence, no desired product was observed. Preliminary results from DNA thermal denaturation and circular dichroism titration studies provided evidence of mixture 13a , b binding to the target DNA sequence 5′-TCTCAA-3′.

【 授权许可】

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