D-Val22 containing human big endothelin-1 analog, [D-Val22]Big ET-1[16-38], inhibits the endothelin converting enzyme. 1994

A Morita, and M Nomizu, and M Okitsu, and K Horie, and H Yokogoshi, and P P Roller
Laboratory of Nutritional Biochemistry, School of Food and Nutritional Sciences, University of Shizuoka, Japan.

Endothelin converting enzyme (ECE) is essential for generation of the biological effects of endothelin-1 (ET-1) from a precursor, big endothelin-1 (Big ET-1). We synthesized four analogs of human Big ET-1[16-38], substituted with single D-amino acids at P1, P2, P1' and P2' positions. ECE activity was determined using an ET-1 specific radioimmunoassay system. None of the D-amino acid containing Big ET-1 analogs were apparently cleaved by ECE, however, one of the synthetic peptides, [D-Val22]Big ET-1[16-38], strongly inhibited the ECE activity. Furthermore, when this D-Val22 containing peptide was preadministered to rat striatum, it was found to inhibit the dopamine release induced by Big ET-1. This result suggests that the D-Val22 containing peptide inhibits the ECE activity in vivo. The D-Val22 containing inhibitor offers hope of developing more potent and highly specific ECE inhibitors of therapeutic significance.

UI MeSH Term Description Entries
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011498 Protein Precursors Precursors, Protein
D011863 Radioimmunoassay Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. Radioimmunoassays
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072396 Endothelin-Converting Enzymes Metalloendopeptidases which convert BIG ENDOTHELIN to ENDOTHELIN-1. ECE-1beta,Endothelin Converting Enzyme,Endothelin Converting Enzyme-1a,Endothelin-Converting Enzyme,Endothelin-Converting Enzyme 1,Endothelin-Converting Enzyme 2,Endothelin-Converting Enzyme II,Endothelin-Converting Enzyme-1b,Endothelin-Converting Metalloprotease 2,Metalloprotease ECE-2,ECE-2, Metalloprotease,Endothelin Converting Enzyme 1,Endothelin Converting Enzyme 1a,Endothelin Converting Enzyme 1b,Endothelin Converting Enzyme 2,Endothelin Converting Enzyme II,Endothelin Converting Enzymes,Endothelin Converting Metalloprotease 2,Metalloprotease ECE 2

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