Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/118413
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Type: Journal article
Title: The role of N-terminal heterocycles in hydrogen bonding to α-chymotrypsin
Other Titles: The role of N-terminal heterocycles in hydrogen bonding to alpha-chymotrypsin
Author: Schumann, N.
Bruning, J.
Marshall, A.
Abell, A.
Citation: Bioorganic and Medicinal Chemistry Letters, 2019; 29(3):396-399
Publisher: Elsevier
Issue Date: 2019
ISSN: 0960-894X
1464-3405
Statement of
Responsibility: 
Nicholas C.Schumann, John Bruning, Andrew C.Marshall, Andrew D.Abell
Abstract: A series of dipeptide aldehydes containing different N-terminal heterocycles was prepared and assayed in vitro against α-chymotrypsin to ascertain the importance of the heterocycle in maintaining a β-strand geometry while also providing a hydrogen bond donor equivalent to the backbone amide nitrogen of the surrogate amino acid. The dipeptide containing a pyrrole constraint (10) was the most potent inhibitor, with >30-fold improved activity over dipeptides which lacked a nitrogen hydrogen bond donor (namely thiophene 11, furan 12 and pyridine 13). Molecular docking studies of 10 bound to α-chymotrypsin demonstrates a hydrogen bond between the pyrrole nitrogen donor and the backbone carbonyl of Gly216 located in the S3 pocket which is proposed to be critical for overall binding.
Keywords: Chymotrypsin
Heterocycles
Peptidic aldehydes
Peptidomimetic
Protease inhibitors
β-Strand
Rights: © 2018 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.bmcl.2018.12.032
Grant ID: http://purl.org/au-research/grants/arc/CE140100003
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Physics publications

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