Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of novel series of synthetic inhibitors with various serine proteases (leukocyte elastase, thrombin, cathepsin G, chymotrypsin, plasminogen activators and plasmin) and an aspartic protease (HIV-1 protease) were studied. Various aspects were analyzed: mechanism of action, structure-activity relationships, and in some cases, molecular modelling and biological evaluation. Functionalized cyclopeptides and N-aryl azetidin-2-ones behaved as suicide substrates acting specifically on trypsin-like proteases (thrombin or urokinase) and elastases, respectively. Novel hydrazinopeptides acted as reversible inhibitors of elastases. Coumarin derivatives inactivated very efficiently chymotrypsin-like proteases (k(inact)/K(I) = 760,000 M(-1) .s(-1)). Inhibitors of HIV-1 protease acting either as inactivators or dimerization inhibitors are under investigation. The inhibitors described above are useful for elucidating the biological roles of the target enzymes and constitute potential drugs.
 ...
PMID:[Synthetic inhibitors targeting serine and aspartic acid proteases]. 877 49

We introduce a simple theoretical approach for an equilibrium study of proteins with known native-state structures. We test our approach with results on well-studied globular proteins, chymotrypsin inhibitor (2ci2), barnase, and the alpha spectrin SH3 domain, and present evidence for a hierarchical onset of order on lowering the temperature with significant organization at the local level even at high temperatures. A further application to the folding process of HIV-1 protease shows that the model can be reliably used to identify key folding sites that are responsible for the development of drug resistance.
 ...
PMID:Conformations of proteins in equilibrium. 1149 84

Aza-peptide epoxides, a novel class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. Aza-peptide epoxides with an aza-Asp residue at P1 are excellent irreversible inhibitors of caspases-1, -3, -6, and -8 with second-order inhibition rates up to 1 910 000 M(-1) s(-1). In general, the order of reactivity of aza-peptide epoxides is S,S > R,R > trans > cis. Interestingly, some of the R,R epoxides while being less potent are actually more selective than the S,S epoxides. Our aza-peptide epoxides designed for caspases are stable, potent, and specific inhibitors, as they show little to no inhibition of other proteases such as the aspartyl proteases porcine pepsin, human cathepsin D, plasmepsin 2 from P. falciparum, HIV-1 protease, and the secreted aspartic proteinase 2 (SAP-2) from Candida albicans; the serine proteases granzyme B and alpha-chymotrypsin; and the cysteine proteases cathepsin B and papain (clan CA), and legumain (clan CD).
 ...
PMID:Design, synthesis, and evaluation of aza-peptide epoxides as selective and potent inhibitors of caspases-1, -3, -6, and -8. 1499 41

New 2-bromomethyl-8-substituted-benzo[c]chromen-6-ones have been synthesized and their bioactive properties have been evaluated on different enzymatic models: serine proteases (trypsin and alpha-chymotrypsin), HIV aspartyl protease, nitric oxide synthase and a panel of protein kinases. These new derivatives can provide upon chemical or enzymatic attack, very reactive quinonimine methide intermediates, which could be utilized for the design of enzyme inhibitors. We found that some of these new derivatives exhibit modest inhibitory activities on the studied enzyme models, but it could be improved after structure optimization.
 ...
PMID:New 2-bromomethyl-8-substituted-benzo[c]chromen-6-ones. Synthesis and biological properties. 1558 26

The PROPKA method for the prediction of the pK(a) values of ionizable residues in proteins is extended to include the effect of non-proteinaceous ligands on protein pK(a) values as well as predict the change in pK(a) values of ionizable groups on the ligand itself. This new version of PROPKA (PROPKA 2.0) is, as much as possible, developed by adapting the empirical rules underlying PROPKA 1.0 to ligand functional groups. Thus, the speed of PROPKA is retained, so that the pK(a) values of all ionizable groups are computed in a matter of seconds for most proteins. This adaptation is validated by comparing PROPKA 2.0 predictions to experimental data for 26 protein-ligand complexes including trypsin, thrombin, three pepsins, HIV-1 protease, chymotrypsin, xylanase, hydroxynitrile lyase, and dihydrofolate reductase. For trypsin and thrombin, large protonation state changes (|n| > 0.5) have been observed experimentally for 4 out of 14 ligand complexes. PROPKA 2.0 and Klebe's PEOE approach (Czodrowski P et al. J Mol Biol 2007;367:1347-1356) both identify three of the four large protonation state changes. The protonation state changes due to plasmepsin II, cathepsin D and endothiapepsin binding to pepstatin are predicted to within 0.4 proton units at pH 6.5 and 7.0, respectively. The PROPKA 2.0 results indicate that structural changes due to ligand binding contribute significantly to the proton uptake/release, as do residues far away from the binding site, primarily due to the change in the local environment of a particular residue and hence the change in the local hydrogen bonding network. Overall the results suggest that PROPKA 2.0 provides a good description of the protein-ligand interactions that have an important effect on the pK(a) values of titratable groups, thereby permitting fast and accurate determination of the protonation states of key residues and ligand functional groups within the binding or active site of a protein.
 ...
PMID:Very fast prediction and rationalization of pKa values for protein-ligand complexes. 1849 3