20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease

Authors :: Sayaka Nagata
Masaji Tamura
Kumiko Yoshizawa-Kumagaye
Joji Kato
Mariko Tokashiki
Goro Miki
Taku Yoshiya
Kazuo Kitamura
Shinya Ashizuka
Nobuko Kuroishi
Motoo Yamasaki
Source :: Gastrointestinal Disorders, Vol 2, Iss 33, Pp 366-377 (2020), Gastrointestinal Disorders, Volume 2, Issue 4, Pages 33-377
Publication Year :: 2020
Publisher :: MDPI AG, 2020.
Abstract: Human adrenomedullin (AM), a hypotensive peptide, also has anti-colitis activity. We prepared a polyethylene glycol (PEG) ylated form of AM through the conjugation of PEG-AM (1&ndash<br />15) and AM (15&ndash<br />52). Highly pure monomeric 20 kDa PEG-AM (20kPEG-AM) stimulated cyclic adenosine monophosphate production in HEK-293 cells stably expressing the type 1 AM receptor in a dose-dependent manner. The half-life of 20kPEG-AM was 7.4 h following subcutaneous administration in mice. We assessed the anti-colitis effect of subcutaneous 20kPEG-AM administration in the dextran sodium sulfate murine colitis model. Single and double subcutaneous injection of 20kPEG-AM significantly reduced total inflammation scores. These results suggest that 20kPEG-AM is a promising therapeutic candidate for the treatment of human inflammatory bowel diseases.

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