title: Beta-amino acid analogs of an insect neuropeptide feature potent bioactivity and resistance to peptidase hydrolysis.
abstract: Insect neuropeptides of the insect kinin class share a common C-terminal pentapeptide sequence F(1)X(1)(2)X(2)(3)W(4)G(5)-NH(2) (X(2)(3) = P, S, A) and regulate such critical physiological processes as water balance and digestive enzyme release. Analogs of the insect kinin class, in which the critical residues of F(1), P(3), and W(4) were replaced with beta(3)-amino acid or their beta(2)-homo-amino acid variants, have been synthesized by the solid phase peptide strategy. The resulting single- and double-replacement analogs were evaluated in an insect diuretic assay and enzyme digestion trials. Analogs modified in the core P(3) position produce a potent and efficacious diuretic response that is not significantly different from that obtained with the endogenous achetakinin peptides. The analogs also demonstrate enhanced resistance to hydrolysis by ACE and NEP, endopeptidases that inactivate the natural insect neuropeptides. This paper describes the first instance of beta-amino acids analogs of an arthropod peptide that demonstrate significant bioactivity and resistance to peptidase degradation.
authors.affiliation: Areawide Pest Management Research Unit, Southern Plains Agricultural Research Center, U.S. Department of Agriculture, 2881 F/B Road, College Station, TX, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Zubrzak
authors.forename: Howard
authors.initials: H
authors.lastname: Williams
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Coast
authors.forename: R Elwyn
authors.initials: RE
authors.lastname: Isaac
authors.forename: Gloria
authors.initials: G
authors.lastname: Reyes-Rangel
authors.forename: Eusebio
authors.initials: E
authors.lastname: Juaristi
authors.forename: Janusz
authors.initials: J
authors.lastname: Zabrocki
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Nachman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001704:Biopolymers / Q000737:chemistry / Q000494:pharmacology; D006135:Gryllidae; D006868:Hydrolysis; D066298:In Vitro Techniques; D019476:Insect Proteins / Q000737:chemistry* / Q000494:pharmacology*; D008317:Malpighian Tubules / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D009479:Neuropeptides / Q000737:chemistry* / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010447:Peptide Hydrolases
chemical_list: D001704:Biopolymers; D019476:Insect Proteins; D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D010447:Peptide Hydrolases