Yayoi Nishimoto, Sayaka Nagata, Emiko Akashi, Motoo Yamasaki, Kazuo Kitamura
Biochemical and biophysical research communications 2020 Aug 27Human 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. Copyright © 2020. Published by Elsevier Inc.
Yayoi Nishimoto, Sayaka Nagata, Emiko Akashi, Motoo Yamasaki, Kazuo Kitamura. Thrombin rapidly digests adrenomedullin: Synthesis of adrenomedullin analogs resistant to thrombin. Biochemical and biophysical research communications. 2020 Aug 27;529(3):778-783
PMID: 32736707
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