Study on superagonist and antagonist of brain-gut peptide

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Studies on superagonist and antagonist of brain-gut peptideThe aim of the present study was to develop newly designed super agonist and antagonist of brain-gut peptide.1) Structure-function studies on galanin reveled that the galanin amin-terminal 1-15 sequence is crucial for its activity in several bioassay system. In order to develop galanin antagonist, we have examined several galanin analogs, which were newly synthesiged. Among them.[D-Thr^6, D-Trp^<8,9>]galanin(1-15)-ol was found to act as a galanin antogonist on glucose-induced insulin release in vitro.2) Total synthesis of human glicentin comprising 69 amino acid residues was completed. In addition, structure-function studies on glucagon-related peptides revealed that glucagon-like peptide(GLP)1(7-33)as well as GLP-1(7-37) and GLP-1(7-36)amide showed potent insulinotropic activity, suggesting that major active site of GLP-1 resides in the 7-33 sequence.3) Using PACAP C-terminal fragment such as PACAP(5-38), which is newly discovered PACAP antagonist, PACAP receptor and helodermin-affinity receptor were clearly characterized.4) Purposely designed PTHrP(7-34)analog such as[desamino-Leu^8, Asn^<10>, Leu^<11>, D-Trp^<12>]PTHrP(8-34)NH_2 was found to be a potent PTHrP antagonist in vitro and in vivo.5) Radioimmunoassay specific for chromogranin A was developed. This assay system was shown to be useful for brain-gut peptide research.