title: Hydrolysis of thymic humoral factor gamma 2 by neutral endopeptidase (EC 3.4.24.11).
abstract: A search for the natural substrates for neutral endopeptidase (NEP; EC 3.4.24.11) in the immune system led to investigation of the enzyme's action on thymic humoral factor gamma 2 (THF). The ectoenzyme rapidly and efficiently hydrolyses the Lys6-Phe7 bond of the octapeptide. The site of cleavage was confirmed by h.p.l.c. analysis, amino acid analysis and sequence determination of the products. Phosphoramidon (3.6 microM), a potent inhibitor of the enzyme, prevents this cleavage even during prolonged incubation. The high efficiency of hydrolysis of THF by NEP is similar to that reported for [Leu5]enkephalin, and the dipeptide Phe-Leu is the C-terminal product in the hydrolysis of both peptides. The presence of NEP, reportedly identified as the common acute lymphoblastic leukaemia antigen (CALLA), in bone-marrow cells and other cells of the immune system raises the possibility that it may play a role in modulating the activity of peptides such as THF.
authors.affiliation: Sackler Institute of Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: F E
authors.initials: FE
authors.lastname: Indig
authors.forename: M
authors.initials: M
authors.lastname: Pecht
authors.forename: N
authors.initials: N
authors.lastname: Trainin
authors.forename: Y
authors.initials: Y
authors.lastname: Burstein
authors.forename: S
authors.initials: S
authors.lastname: Blumberg
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D007700:Kinetics; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D009842:Oligopeptides; C064563:thymic humoral factor gamma 2; D015260:Neprilysin