HPLC and PDMS analysis of cleavage products aid in the design of small, stable ANP analogues.
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.
Devine
E M
EM
Cardiovascular Research Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Buko
A M
AM
Cepa
S P
SP
Davidsen
S K
SK
Holleman
W H
WH
Marselle
C A
CA
Opgenorth
T J
TJ
Rockway
T W
TW
von Geldern
T W
TW
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
D010455:Peptides; C066680:A 68828; D009320:Atrial Natriuretic Factor