Chemical and biomimetic total syntheses of natural and engineered MCoTI cyclotides

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 P1 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-microM inhibitor of foot-and-mouth-disease virus (FMDV) 3C protease, the first reported peptide-based inhibitor of this important viral enzyme.     

Synthesis and incorporation into cyclic peptides of tolan amino acids and their hydrogenated congeners: construction of an array of A-B-loop mimetics of the Cε3 domain of human IgE

The disruption of the human immunolobulin E-high affinity receptor I (IgE-FcεRI) protein-protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A-B loop within the Cε3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC(50) ～660 μM) is displayed by the peptide containing a 2,2'-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A-B loop epitope in IgE.     

Total synthesis of the macrocyclic cysteine knot microprotein MCoTI-II

The first total synthesis of MCoTI-II, a cysteine knot microprotein and potent trypsin inhibitor, is described; a synthetic strategy has been developed that combines efficient backbone construction via optimised solid phase peptide synthesis with one-pot 'thia-zip' native chemical ligation and refolding to yield the natural product.     

FTIR Emission Spectra, Molecular Constants, and Potential Curve of Ground State GeO

Extensive new high-temperature, high-resolution FTIR emission spectroscopy measurements for the five common isotopomers of GeO are combined with previous diode laser and microwave measurements in combined isotopomer analyses. New Dunham expansion parameters and an accurate analytical potential energy function are determined for the ground X1Sigma+ state. Copyright 1999 Academic Press.