118380-06-6Relevant articles and documents
P4 cap modified tetrapeptidyl α-ketoamides as potent HCV NS3 protease inhibitors
Sun, David X.,Liu, Lifei,Heinz, Beverly,Kolykhalov, Alexander,Lamar, Jason,Johnson, Robert B.,Wang, Q. May,Yip, Yvonne,Chen, Shu-Hui
, p. 4333 - 4338 (2007/10/03)
We describe herein the design, syntheses, and biological evaluation of new series of P4 tetrazole and adipic acid, ester, amide capped tetrapeptidyl α-ketoamide based HCV protease inhibitors.
Specificity of DNA alkylation by 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes depends on the structure of the acyl group: Kinetic and product studies
Smith,Schmidt,Czerwinski,Taneyhill,Snyder,Kline,Michejda,Smith Jr.
, p. 466 - 475 (2007/10/03)
The reactions of calf thymus DNA with ten 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes of varying acyl side chain structure were studied alone, or in the presence of porcine liver esterase in pH 7.0 phosphate buffer. In several of the key triazenes, the acyl substituent contained a free carboxylic acid group. With esterase present in the reaction mixture, the resultant levels of DNA alkylation could be correlated with the kinetic rates of decomposition of the triazenes. Under these conditions, the predominant pathway of decomposition involved deacylation of the parent triazene and eventual production of an alkanediazonium ion. This intermediate subsequently alkylated DNA-guanine to give 7-alkylguanine as the principal reaction product. In the absence of esterase, the order of DNA alkylation for all of the acyltriazenes did not correlate with their respective rates of decomposition, leading to the conclusion that the triazenes did not decompose by the expected mode of uncatalyzed N(2)-N(3) heterolyic cleavage. The major DNA alkylation product from the N(3)-methyltriazenes was 7-methylguanine, instead of the expected 7-(chloroethyl)- and 7-(hydroxyethyl)guanine products, which suggested that the acyl group was being hydrolyzed. However, acyltriazenes with an N(3)-benzyl group rather than a methyl in this position produced very little 7-benzylguanine product, contrary to prediction. An alternative mechanism involving internally assisted hydrolysis of the side chain ester is proposed to explain these results. NMR product analysis and computational studies were carried out to lend support to the postulated mechanism.
Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor
Biessen, Erik A.L.,Beuting, Diana M.,Roelen, Harlof C.P.F.,Marel, Gijs A. van de,Boom, Jacques H. van,Berkel, Theo J.C. van
, p. 1538 - 1546 (2007/10/02)
High-affinity ligands for the asialoglycoprotein receptor, which is uniquely localized on the parenchymal liver cell and recognizes oligoantennary galactosides, might be utilized as homing device to specifically target drugs or genes to paranchymal liver
Antibody combining sites that exhibit stereoselective synthase activity, and methods using the same
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, (2008/06/13)
A phosphorus-containing analog-ligand having a stereoconfiguration that substantially corresponds to the stereoconfiguration of an amide- or ester-forming transition state is used to induce production of receptor molecules whose antibody combining sites have stereospecific amide or ester synthase catalytic activity when reacted with a ligand containing (i) a carbonyl carbon atom and (ii) an amine or alcohol group that are structurally capable of forming a preselected stereoisomer of a carboxylic amide or ester.
Antibodies which catalyze hydrolysis of ester bonds
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, (2008/06/13)
An analog-ligand having a conformation that substantially corresponds to the conformation of a hydrolytic transition state of an amide or ester reactant ligand is used to produce receptor molecules of predetermined specificity. The receptor molecules include an antibody combining site that binds to a reactant ligand and thereby stabilizes the tetrahedral carbon atom of the amide or ester hydrolysis transition state of that reactant ligand to catalytically hydrolyze the reactant ligand at a predetermined site.
Antibody combining sites that exhibit amide or ester synthase activity
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, (2008/06/13)
A phosphorous-containing analog-ligand having a conformation that substantially corresponds to the conformation of an amide- or ester-forming transition state is used to induce production of receptor molecules whose antibody combining sites have amide or ester synthase catalytic activity when reacted with a ligand containing (i) a carbonyl carbon atom and (ii) an amine or alcohol group that are structurally capable of forming a preselected carboxylic amide or ester bond.