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Synlett 2017; 28(15): 1901-1906
DOI: 10.1055/s-0036-1588840
DOI: 10.1055/s-0036-1588840
cluster
Divergent Protein Synthesis of Bowman–Birk Protease Inhibitors, their Hydrodynamic Behavior and Co-crystallization with α-Chymotrypsin
Weitere Informationen
Publikationsverlauf
Received: 28. März 2017
Accepted after revision: 30. April 2017
Publikationsdatum:
24. Mai 2017 (online)
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.
Key words
protein synthesis - divergent synthesis - Bowman–Birk protease inhibitor - X-ray crystallography - α-chymotrypsin - native chemical ligationSupporting Information
- Experimental details, compound characterization, enzyme inhibition and DLS measurements. Crystal structure coordinates and structure factors have been deposited in PDB entries 5J4Q (BBI (1):α-chymotrypsin) and 5J4S (11:α-chymotrypsin).Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1588840.
- Supporting Information
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References and Notes
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