期刊
ORGANIC & BIOMOLECULAR CHEMISTRY
卷 6, 期 8, 页码 1462-1470出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/b801667d
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资金
- Biotechnology and Biological Sciences Research Council [BB/D02014X/1] Funding Source: Medline
- BBSRC [BB/D02014X/1] Funding Source: UKRI
The naturally-occurring cyclic cystine-knot microprotein trypsin inhibitors MCoTI-I and MCoTI-II have been synthesised using both thia-zip native chemical ligation and a biomimetic strategy featuring chemoenzymatic cyclisation by an immobilised protease. Engineered analogues have been produced containing a range of substitutions at the P-1 position that redirect specificity towards alternative protease targets whilst retaining excellent to moderate affinity. Furthermore, we report an MCoTI analogue that is a selective low-mu M inhibitor of foot-and-mouth-disease virus (FMDV) 3C protease, the first reported peptide-based inhibitor of this important viral enzyme.
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