Synthesis and Functional Characterization of Tridegin and Its Analogues: Inhibitors and Substrates of Factor XIIIa
Synthesis and Functional Characterization of Tridegin and Its Analogues: Inhibitors and Substrates of Factor XIIIa
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DOI：
10.1002/cmdc.201100405
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发表时间：
2012-02-06
期刊：
影响因子：
3.4
通讯作者：
Imhof, Diana
中科院分区：
文献类型：
--
作者：
Boehm, Miriam;Kuehl, Toni;Imhof, Diana
Tridegin是从水蛭Haementeria ghilianii中分离出来的一种66聚肽，是一种有效的凝血因子XIIIa抑制剂。本文介绍了三聚氰胺的两种不同的合成策略：固相组装和天然化学连接，然后在溶液中氧化。我们检测了Tridegin和截断的类似物的活性，并揭示了亲本肽的c端区域的特别重要性。基于这些研究，可以确定抑制因子XIIIa所需的最小序列。我们的数据显示，tridegin第52位（Q52）的谷氨酰胺残基很可能与XIIIa因子的活性位点结合，因此可能与该酶发生反应。n端区域的功能也被讨论，因为分离的tridegin的c端片段在因子XIIIa存在下迅速失去其抑制活性，而全长抑制剂则不是这样。
Tridegin, a 66-mer peptide isolated from the leech Haementeria ghilianii, is a potent inhibitor of the coagulation factor XIIIa. This paper describes the chemical synthesis of tridegin by two different strategiessolid-phase assembly and native chemical ligationboth followed by oxidation in solution phase. Tridegin and truncated analogues were examined for their activity and revealed a particular importance of the C-terminal region of the parent peptide. Based on these studies a minimal sequence required for factor XIIIa inhibition could be identified. Our data revealed that the glutamine residue at position 52 (Q52) of tridegin most likely binds to the active site of factor XIIIa and was therefore suggested to react with the enzyme. The function of the N-terminal region is also discussed, as the isolated C-terminal segment of tridegin lost its inhibitory activity rapidly in the presence of factor XIIIa, whereas this was not the case for the full-length inhibitor.