32943-08-1Relevant academic research and scientific papers
Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: A strategy for the design of peptidase inhibitors
Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Law, James K.,Marabout, Benoit,Luthra, Pratibha Mehta,Moore, Andrew N. J.,Peschard, Olivier,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
, p. 664 - 674 (2007/10/03)
The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO3H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH2. In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 μM) and Ala-Pro-Ala-OH (K(i) = 3 μM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 μM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 μM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.
Cytotoxic N,N'-bis (succinyl-peptide-) derivatives of 1,4-bis (aminoalkyl)-5,8-dihydroxyanthraquinones and antibody conjugates thereof
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, (2008/06/13)
The present invention is concerned with novel N,N'-bis(succinyl-peptide)-derivatives of 1,4-bis(aminoalkyl)-5,8-dihydroxyanthraquinones and the corresponding antibody conjugates thereof each of which have potential use in the treatment of human carcinomas.
Antitumor amino acid and peptide derivatives of 1,4-bis(aminoalkyl and hydroxy-aminoalkyl)amino)-5,8-dihydroxyanthraquinones
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, (2008/06/13)
Antitumor amino acid and peptide derivatives of 1,4-bis[(aminoalkyl and hydroxyaminoalkyl)amino]-5,8-dihydroxyanthraquinones.
New compounds: Peptide derivatives of the antitumor agent N-phosphonoacetyl-L-aspartic acid
Gigot,Penninckx
, p. 275 - 277 (2007/10/02)
Two peptide forms of the antitumor transition state analogue N-phosphonoacetyl-L-aspartic acid (N2-phosphonoacetyl-N4-glycylglycinamidoethyl-L-asparagine and N1-glycylglycinamidoethyl-N2-phosphonoacetyl-L-isoasparagine) have been synthesized to obtain potential medicinal agents useful as prodrugs or in a lysosomotropic carrier approach. The bridging unit, ethylenediamine, used for synthetic purposes might be of general interest.
