title: HPLC and PDMS analysis of cleavage products aid in the design of small, stable ANP analogues.
abstract: The degradation of a prototypical small analogue of atrial natriuretic peptide (ANP) has been studied using HPLC and mass spectrometric techniques. These studies revealed that removal of the N-terminal amino acid was the primary catabolic event in vitro. Based on this information the N-terminus was remanufactured to provide a family of more stable analogues. Additional stabilization was provided through modification of the C-terminal tripeptide. Through dramatically more stable in vitro, these new analogues do not appear to have longer in vivo half-lives.
authors.affiliation: Cardiovascular Research Division, Abbott Laboratories, Abbott Park, Illinois 60064.
authors.forename: E M
authors.initials: EM
authors.lastname: Devine
authors.forename: A M
authors.initials: AM
authors.lastname: Buko
authors.forename: S P
authors.initials: SP
authors.lastname: Cepa
authors.forename: S K
authors.initials: SK
authors.lastname: Davidsen
authors.forename: W H
authors.initials: WH
authors.lastname: Holleman
authors.forename: C A
authors.initials: CA
authors.lastname: Marselle
authors.forename: T J
authors.initials: TJ
authors.lastname: Opgenorth
authors.forename: T W
authors.initials: TW
authors.lastname: Rockway
authors.forename: T W
authors.initials: TW
authors.lastname: von Geldern
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D004355:Drug Stability; D006207:Half-Life; D007668:Kidney / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits
chemical_list: D010455:Peptides; C066680:A 68828; D009320:Atrial Natriuretic Factor