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Identification of a degrading enzyme in human serum that hydrolyzes a C‐terminal core sequence of neuromedin U
Author(s) -
Takayama Kentaro,
Taguchi Akihiro,
Yakushiji Fumika,
Hayashi Yoshio
Publication year - 2016
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22770
Subject(s) - chemistry , terminal (telecommunication) , enzyme , sequence (biology) , biochemistry , identification (biology) , hydrolysis , core (optical fiber) , computational biology , biology , botany , telecommunications , materials science , computer science , composite material
Neuromedin U (NMU), an anorexigenic peptide, has attracted attention as a candidate for development of drugs against obesity. We recently developed several potent hexapeptidic agonists derived from NMU that share a common Pro‐Arg‐Asn‐NH 2 (PRN) sequence at their C‐termini and found that the amide bond between Arg and Asn is rapidly degraded in serum. In this study, we determined that the key enzyme responsible for this biodegradation was thrombin. Both irreversible and reversible thrombin inhibitors (PPACK and argatroban, respectively) enhanced the serum stability of both hexapeptidic agonists and human NMU itself as an inherent ligand. In addition, rapid degradation did not occur in citrated human plasma because thrombin was not activated under these conditions. Furthermore, we found that an N‐terminal 2‐thienylacetyl group in hexapeptidic agonists enhanced recognition by thrombin. These findings will be valuable for future investigations of the biological functions of NMU in vivo. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 440–445, 2016.