Degradation of brain natriuretic peptide by neutral endopeptidase: species specific sites of proteolysis determined by mass spectrometry.
Brain natriuretic peptide (BNP) from 3 different species was cleaved by neutral endopeptidase (NEP) and the products separated by HPLC. The newly formed products were identified by fast atom bombardment or nebulizer-assisted electrospray mass spectrometry to elucidate the sites of proteolysis. Porcine BNP was cleaved at the Arg8-Leu9 and Ser14-Leu15 bonds. Rat BNP was cleaved at the Arg23-Leu24 and Arg30-Leu31 bonds. Human BNP was cleaved at the Pro2-Lys3, Met4-Val5 and Arg17-Leu18 bonds. The Cys-Phe bond which is present in all species of BNP is not cleaved by NEP.
Norman
J A
JA
Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey.
Little
D
D
Bolgar
M
M
Di Donato
G
G
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000032:analysis; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D013058:Mass Spectrometry; D008961:Models, Structural; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D015260:Neprilysin / Q000302:isolation & purification / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification; D011487:Protein Conformation; D051381:Rats; D013045:Species Specificity; D013379:Substrate Specificity; D013552:Swine
D004220:Disulfides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D020097:Natriuretic Peptide, Brain; D015260:Neprilysin