Positional effects of click cyclization on β-hairpin structure, stability, and function.
Positional effects of click cyclization on β-hairpin structure, stability, and function.
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DOI：
10.1039/c2ob26445e
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发表时间：
2013-01-07
影响因子：
3.2
通讯作者：
Waters ML
中科院分区：
文献类型：
--
作者：
Park JH;Waters ML
使用铜 (I) 辅助的叠氮-炔环加成（CuAAC，或“点击”反应）作为 β-发夹稳定的方法，在几个不同的位置进行了研究，以确定对发夹结构和功能的影响，包括氢键位点、非氢键位点和肽末端。还研究了转角序列在肽中的作用和叠氮化物的链长度。经确定，CuAAC 反应是锁定具有 I' 型转角（VNGO）和 II' 型转角（VpGO）的肽中的 β-发夹结构的合适方法。此外，与非环状肽相比，所有环状变体都表现出改善的热稳定性和抗蛋白水解性，无论链中的位置如何。此外，CuAAC 环化肽的功能没有改变，如与 WKWK 肽相似的 ATP 结合亲和力所显示的。这些研究为β-发夹肽的CuAAC环化提供了一种综合方法，可进一步用于抑制蛋白质-蛋白质和蛋白质-核酸相互作用。
The use of the copper (I)-assisted azide-alkyne cycloaddition (CuAAC, or “click” reaction) as a method of β-hairpin stabilization was investigated at several different positions to determine the impact on hairpin structure and function, including hydrogen bonded sites, non-hydrogen bonded sites, and at the peptide termini. The role of the turn sequence in the peptide and the chain length of the azied were also investigated. It was determined that the CuAAC reaction was a suitable method for locking in β-hairpin structure in peptides possessing either the type I’ turn, VNGO and the type II’ turn, VpGO. Moreover, all cyclic variants exhibited improved thermal stability and resistance to proteolysis as compared to the non-cyclic peptides, regardless of the position in the strand. Additionally, the function of the CuAAC cyclized peptides was not altered as exhibited by similar binding affinities for ATP as the WKWK peptide. These studies provided a comprehensive method for CuAAC cyclization of β-hairpin peptides, which could further be utilized in the inhibition of protein-protein and protein-nucleic acid interactions.
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