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)

13C NMR and mass spectrometry studies have been used to demonstrate that the inhibition of alpha-chymotrypsin by N-sulfonylhydroxymethylpyrrole inhibitors (10) is non-covalent. Hydroxyalkylpyrroles in which an electron-withdrawing group (acyl substituent) is introduced at the alternative C2 position have been synthesised and also shown to inactivate alpha-chymotrypsin. SAR studies on this class suggests that the incorporation of phenylalanine at C2 is favoured, however, there is little gain in introducing a hydrophobic substituent at C5.
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PMID:Ring-deactivated hydroxyalkylpyrrole-based inhibitors of alpha-chymotrypsin: synthesis and mechanism of action. 1294 1

Through high throughput screening of various libraries, substituted styryl naphthalene 6 was identified as an HCMV protease inhibitor. Optimization of various regions of the lead molecule using parallel synthesis resulted in 1,6-substituted naphthalenes 19d-i. These compounds displayed good potency and were selective over elastase, trypsin, and chymotrypsin. The optimization approach on lead compound 6 in three different regions of the molecule using parallel solution-phase synthesis and the corresponding SAR are discussed in detail.
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PMID:Design and syntheses of 1,6-naphthalene derivatives as selective HCMV protease inhibitors. 1505 90

Bioassay-guided fractionation of the polar extract of a Microcystis aeruginosa water bloom biomass yielded 10 micropeptins and one anabaenopeptin. Eight of the micropeptins, micropeptins HU1069 (1), HU989 (2), HU1021 (3), HU1041 (4), HU975 (5), HU895A (6), HU909 (7), and HU895B (8), are new, while two, micropeptins 478-A (10) and 478-B (11), were previously isolated from a bloom of M. aeruginosa from Japan. The new anabaenopeptin HU892 (9) belongs to the relatively rare subgroup, presenting an aliphatic amino acid at the carboxylic end of the peptide and N-methylhomoaromatic amino acid at the second position. The structures of the compounds were determined by 1D and 2D NMR techniques and mass spectrometric data. The isolated micropeptins inhibited trypsin with IC(50)'s that varied between 0.7 and 5.2 microM and unexpectedly inhibited chymotrypsin with IC(50)'s that varied between 2.8 and 72.0 microM. The SAR of these micropeptins is discussed.
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PMID:Protease inhibitors from a water bloom of the cyanobacterium Microcystis aeruginosa. 1965 Jun 39

Seven new natural products, micropeptin MZ845 (1), micropeptin MZ859 (2), micropeptin MZ939A (3), micropeptin MZ925 (4), micropeptin MZ939B (5), micropeptin MZ1019 (6), and micropeptin MZ771 (7), as well as two known micropeptins, cyanopeptolin S (8) and cyanopeptolin SS (9), were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. that was collected from a fishpond in Kibbutz Ma'ayan Tzvi, Israel, in July 2006. The structures of the pure natural products were elucidated using spectroscopic methods, including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey's method for HPLC. The inhibitory activity of the compounds was determined for the serine proteases: trypsin, chymotrypsin, thrombin, and elastase. These micropeptins inhibited trypsin with IC(50)'s that varied between 0.6 and 24.2 microM. The SAR of these micropeptins is discussed.
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PMID:Micropeptins from an Israeli fishpond water bloom of the cyanobacterium Microcystis sp. 2002 81

Freshwater and terrestrial cyanobacteria resemble the marine forms in producing divergent chemicals such as linear, cyclic and azole containing peptides, alkaloids, cyclophanes, terpenes, lactones, etc. These metabolites have wider biomedical potentials in targeting proteases, cancers, parasites, pathogens and other cyanobacteria and algae (allelopathy). Among the various families of non-marine cyanobacterial peptides reported, many of them are acting as serine protease inhibitors. While the micropeptin family has a preference for chymotrypsin inhibition rather than other serine proteases, the aeruginosin family targets trypsin and thrombin. In addition, cyanobacterial compounds such as scytonemide A, lyngbyazothrins C and D and cylindrocyclophanes were found to inhibit 20S proteosome. Apart from proteases, metabolites blocking the other targets of cancer pathways may exhibit cytotoxic effect. Colon and rectum, breast, lung and prostate are the worst affecting cancers in humans and are deduced to be inhibited by both peptidic and non-peptidic compounds. Moreover, the growth of infections causing parasites such as Plasmodium, Leishmania and Trypanosoma are well controlled by peptides: aerucyclamides A-D, tychonamides and alkaloids: nostocarboline and calothrixins. Likewise, varieties of cyanobacterial compounds tend to inhibit serious infectious disease causing bacterial, fungal and viral agents. Interestingly, portoamides, spiroidesin, nostocyclamide and kasumigamide are the allelopathic peptides determined to suppress the growth of toxic cyanobacteria and nuisance algae. Thus cyanobacterial compounds have a broad bioactive spectrum; the analysis of SAR studies will not only assist to find out the mode of action but also reveal bioactive key components. Thereby, developing the drugs bearing these bioactive skeletons to treat various illnesses is wide open.
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PMID:SAR analysis and bioactive potentials of freshwater and terrestrial cyanobacterial compounds: a review. 2317 44

Bicyclic pyrazinone and pyrimidinone amides were designed and synthesized as potent TF-FVIIa inhibitors. SAR demonstrated that the S2 and S3 pockets of FVIIa prefer to bind small, lipophilic groups. An X-ray crystal structure of optimized compound 9b bound in the active site of FVIIa showed that the bicyclic scaffold provides 5 hydrogen bonding interactions in addition to projecting groups for interactions within the S1, S2 and S3 pockets. Compound 9b showed excellent FVIIa potency, good selectivity against FIXa, Xa, XIa and chymotrypsin, and good clotting activity.
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PMID:Design and synthesis of bicyclic pyrazinone and pyrimidinone amides as potent TF-FVIIa inhibitors. 2341 3