Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1038/aps.2015.59 http://scihub22266oqcxt.onion/10.1038/aps.2015.59 C4561975!4561975!26279158     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Acta+Pharmacol+Sin 2015 ; 36 (9): 1145-50 Nephropedia Template TP {{tp|p=26279158|t=2015. Structural basis for 18-?-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor |pdf=|usr=}}{{26279158}} gab.com Text Structural basis for 18- -glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor JO: Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=26279158 #FOAvip Aim:: Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. Methods:: Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-?-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 Å resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. Results:: A natural compound 18-?-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 ?mol/L and 0.93 ?mol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 ?mol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the ?-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. Conclusion:: This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors. Twit Text FOAVip Structural basis for 18- -glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor ????Acta Pharmacol Sin http://www.kidney.de/pget.php?&tw=1&pmid=26279158 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26279158 #FOAvip English Wikipedia <ref>{{Cite pmid|26279158}}</ref> Structural basis for 18-?-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor #MMPMID26279158 Zhang H; Huang Q; Zhai J; Zhao Yn; Zhang Lp; Chen Yy; Zhang Rw; Li Q; Hu Xp Acta Pharmacol Sin 2015[Sep]; 36 (9): 1145-50 PMID26279158show ga Aim:: Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. Methods:: Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-?-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 Å resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. Results:: A natural compound 18-?-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 ?mol/L and 0.93 ?mol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 ?mol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the ?-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. Conclusion:: This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors. äStructural basis for 18-?-glycyrrhetinic acid as a novel non-GSH analo(epmc).pdf DeepDyve Pubget Overpricing