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|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|
|Citation:||Bioorganic and Medicinal Chemistry Letters, 2019; 29(3):396-399|
|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.|
|Rights:||© 2018 Elsevier Ltd. All rights reserved.|
|Appears in Collections:||Aurora harvest 4|
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