title: Silkworm diapause hormone, structure-activity relationships indispensable role of C-terminal amide.
abstract: To determine the structure-activity relationships of the silkworm diapause hormone, a series of peptide analogs having different chain lengths starting from the parent C-terminus and analogs having identical sequences with free acid C-termini were chemically synthesized by solid-phase Fmoc methodology and were further purified by HPLC. Bioassay showed that the analogs with free acid C-termini were non active. The retained activities of those shorter chains were shown only with the amidated C-terminal analogs among which the potency depended on the length of the chain. The active peptides required two minimal elements; namely the sequence near and the amidation of the C-terminus. There was no difference in enzymatic digestion of the C-terminally amidated or free acid analogs in pupal haemolymph. Hence the absence of DH activity of the free acid analogs was not because of being selectively hydrolyzed faster than the C-terminally amidated peptides. This suggested that existence of a certain higher order structure could be involved in expressing hormonal activity, or that the negative charge of the free acid terminus may be deleterious to a proper ligand receptor interaction. Since most of the hydrophobic amino acids were located near the C-terminal portion, both the hydrophobicity of the portion near and the amidation of the C-terminus were indispensable structures for diapause hormone activity.
authors.affiliation: School of Agriculture, Nagoya University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Suwan
authors.forename: M
authors.initials: M
authors.lastname: Isobe
authors.forename: O
authors.initials: O
authors.lastname: Yamashita
authors.forename: H
authors.initials: H
authors.lastname: Minakata
authors.forename: K
authors.initials: K
authors.lastname: Imai
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D012831:Bombyx / Q000378:metabolism*; D002268:Carboxypeptidases / Q000378:metabolism; D043422:Carboxypeptidases A; D006458:Hemolymph / Q000378:metabolism; D007301:Insect Hormones / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: D000577:Amides; D007301:Insect Hormones; D009479:Neuropeptides; D010446:Peptide Fragments; D014867:Water; C075027:diapause hormone; D002268:Carboxypeptidases; D043422:Carboxypeptidases A