title: Potent inhibitors of beta-tryptase and human leukocyte elastase based on the MCoTI-II scaffold.
abstract: MCoTI-II is a member of a class of microproteins known as cyclotides that possess a macrolactam-cystine knot scaffold imparting exceptional physiological stability and structural rigidity. Modification of residues in the active loop and engineered truncations have resulted in MCoTI-II analogues that possess potent activity against two therapeutically significant serine proteases: beta-tryptase and human leukocyte elastase. These results suggest that MCoTI-II is a versatile scaffold for the development of protease inhibitors against targets in inflammatory disease.
authors.affiliation: Department of Chemistry and Chemical Biology Centre, Imperial College London SW7 2AZ, UK.
authors.forename: Panumart
authors.initials: P
authors.lastname: Thongyoo
authors.forename: Camille
authors.initials: C
authors.lastname: Bonomelli
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leatherbarrow
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
mesh_terms: D000595:Amino Acid Sequence; D047169:Cyclotides / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D013379:Substrate Specificity; D053802:Tryptases / Q000037:antagonists & inhibitors*
chemical_list: D047169:Cyclotides; D011480:Protease Inhibitors; C409923:trypsin inhibitor MCoTI-II; D019272:Leukocyte Elastase; D053802:Tryptases