Protease-resistant peptide ligands from a knottin scaffold library.

ABSTRACT: Peptides within the knottin family have been shown to possess inherent stability, making them attractive scaffolds for the development of therapeutic and diagnostic agents. Given its remarkable stability to proteases, the cyclic peptide kalata B1 was employed as a scaffold to create a large knottin library displayed on the surface of E. coli. A library exceeding 10(9) variants was constructed by randomizing seven amino acids within a loop of the kalata B1 scaffold and screened using fluorescence-activated cell sorting to identify peptide ligands specific for the active site of human thrombin. Refolded thrombin binders exhibited high nanomolar affinities in solution and slow dissociation rates and were able to inhibit thrombin's enzymatic activity. Importantly, 80% of a knottin-based thromb

SUBMITTER: Getz JA 

PROVIDER: S-EPMC3158827 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature