Thrombin rapidly digests adrenomedullin: Synthesis of adrenomedullin analogs resistant to thrombin.
Adrenomedullin
Adrenomedullin analog
Bioavailability
Thrombin
cAMP
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
27 08 2020
27 08 2020
Historique:
received:
05
06
2020
accepted:
12
06
2020
entrez:
2
8
2020
pubmed:
2
8
2020
medline:
13
2
2021
Statut:
ppublish
Résumé
Human adrenomedullin (AM) functions as a circulating hormone and as a local paracrine mediator with multiple biological activities. We investigated the metabolism of AM by examining its fragmentation in human serum. Adrenomedullin was rapidly cleaved in human serum, but was relatively stable in plasma. We showed that AM was rapidly digested by thrombin in serum, with AM(13-44) as the main product. On the basis of these data, we prepared AM analogs in which Arg-44 was replaced by Ala, Lys, and D-Arg, respectively. These analogs were resistant to thrombin and showed comparable biological activity to native AM. Furthermore, the bioavailabilities of these peptides were improved after subcutaneous administration in rats. These AM analogs may be promising drug candidates for clinical applications.
Identifiants
pubmed: 32736707
pii: S0006-291X(20)31274-2
doi: 10.1016/j.bbrc.2020.06.057
pii:
doi:
Substances chimiques
ADM protein, human
0
Peptide Fragments
0
Adrenomedullin
148498-78-6
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
778-783Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that Kitamura K. and Yamasaki M. have stocks in Himuka AM Pharma Corporation.