title: Metabolic stability of some tachykinin analogues to cell-surface peptidases: roles for endopeptidase-24.11 and aminopeptidase N.
abstract: The metabolism of several tachykinin antagonists by membrane peptidases has been examined. [beta Ala8]NKA(4-10) was not stabilized against degradation by endopeptidase-24.11 and this was the major activity in renal brush border membranes hydrolyzing this peptide. The antagonist MEN 10263 was much more resistant to hydrolysis by endopeptidase-24.11, although hydrolysis of the C-terminal Leu-Phe bond was detectable. Three other tachykinin receptor antagonists (MEN 10208, MEN 10207, and MEN 10376), by virtue of D-Trp substitutions, were rendered resistant to endopeptidase-24.11 but were still susceptible to aminopeptidase action. These studies provide further insight into design features necessary to produce metabolically stable peptide analogues.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Leeds, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Medeiros
authors.forename: A J
authors.initials: AJ
authors.lastname: Turner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018826:CD13 Antigens / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D005069:Evaluation Studies as Topic; D006868:Hydrolysis; D007668:Kidney / Q000201:enzymology* / Q000648:ultrastructure; D008871:Microvilli / Q000201:enzymology; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000502:physiology*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D013552:Swine; D015320:Tachykinins / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D015320:Tachykinins; C064218:neurokinin A (4-10), beta-Ala(8)-; D015288:Neurokinin A; D018826:CD13 Antigens; D015260:Neprilysin