Synlett 2017; 28(15): 1901-1906
DOI: 10.1055/s-0036-1588840
cluster
© Georg Thieme Verlag Stuttgart · New York

Divergent Protein Synthesis of Bowman–Birk Protease Inhibitors, their Hydrodynamic Behavior and Co-crystallization with α-Chymotrypsin

Christian W. Tornøe*a, Eva Johanssonb, Per-Olof Wahlundc
  • aDepartment of Protein & Peptide Chemistry, Novo Nordisk, Novo Nordisk Park, 2760 Måløv, Denmark   Email: cwet@novonordisk.com
  • bDepartment of Protein & Peptide Structure, Novo Nordisk, Novo Nordisk Park, 2760 Måløv, Denmark
  • cDepartment of Large Protein Biophysics, Novo Nordisk, Novo Nordisk Park, 2760 Måløv, Denmark
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Publication History

Received: 28 March 2017

Accepted after revision: 30 April 2017

Publication Date:
24 May 2017 (eFirst)

Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis

Abstract

A divergent protein synthesis strategy was executed to effectively synthesize Bowman–Birk protease inhibitor (BBI) analogues using native chemical ligation of peptide hydrazides. Grafting selected residues from a potent trypsin inhibitor, sunflower trypsin inhibitor-1, onto the α-chymotrypsin-binding loop of BBI, resulted in a fourfold improvement of α-chymotrypsin inhibition. The crystal structure of a synthetic BBI analogue co-crystallized with α-chymotrypsin confirmed the correct protein fold and showed a similar overall structure to unmodified BBI in complex with α-chymotrypsin. Dynamic light scattering showed that C-terminal truncation of BBI led to increased self-association.

Supporting Information