1. 20 kDa PEGylated Adrenomedullin as a New Therapeutic Candidate for Inflammatory Bowel Disease
- Author
-
Goro Miki, Nobuko Kuroishi, Mariko Tokashiki, Sayaka Nagata, Masaji Tamura, Taku Yoshiya, Kumiko Yoshizawa-Kumagaye, Shinya Ashizuka, Joji Kato, Motoo Yamasaki, and Kazuo Kitamura
- Subjects
adrenomedullin ,polyethylene glycol ,inflammatory bowel disease ,colitis ,dextran sulfate ,Medicine ,Diseases of the digestive system. Gastroenterology ,RC799-869 - 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 (1–15) and AM (15–52). 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.
- Published
- 2020
- Full Text
- View/download PDF