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10.1021/jacs.5b00886 http://scihub22266oqcxt.onion/10.1021/jacs.5b00886 C4405261!4405261!25710634     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Am+Chem+Soc 2015 ; 137 (10): 3678-85 Nephropedia Template TP {{tp|p=25710634|t=2015. Toward a Biorelevant Structure of Protein Kinase C Bound Modulators: Design, Synthesis, and Evaluation of Labeled Bryostatin Analogs for Analysis with REDOR NMR Spectroscopy |pdf=|usr=}}{{25710634}} gab.com Text Toward a Biorelevant Structure of Protein Kinase C Bound Modulators: Design, Synthesis, and Evaluation of Labeled Bryostatin Analogs for Analysis with REDOR NMR Spectroscopy JO: J Am Chem Soc http://www.kidney.de/pget.php?&tw=1&pmid=25710634 #FOAvip Protein kinase C (PKC) modulators are currently of great importance in preclinical and clinical studies directed at cancer, immunotherapy, HIV eradication, and Alzheimer?s disease. However, the bound conformation of PKC modulators in a membrane environment is not known. Rotational Echo Double Resonance (REDOR) NMR spectroscopy could uniquely address this challenge. However, REDOR NMR requires strategically-labeled, high affinity ligands to determine inter-label distances from which the conformation of the bound ligand in the PKC-ligand complex could be identified. Here we report the first computer-guided design and syntheses of three bryostatin analogs strategically-labeled for REDOR NMR analysis. Extensive computer analyses of energetically-accessible analog conformations suggested preferred labeling sites for the identification of the PKC-bound conformers. Significantly, three labeled analogs were synthesized, and, as required for REDOR analysis, all proved highly potent with PKC affinities (~1 nM) on par with bryostatin. These potent and strategically-labeled bryostatin analogs are new structural leads and provide the necessary starting point for projected efforts to determine the PKC-bound conformation of such analogs in a membrane environment, as needed to design new PKC modulators and understand PKC-ligand?membrane structure and dynamics. Twit Text FOAVip Toward a Biorelevant Structure of Protein Kinase C Bound Modulators: Design, Synthesis, and Evaluation of Labeled Bryostatin Analogs for Analysis with REDOR NMR Spectroscopy ????J Am Chem Soc http://www.kidney.de/pget.php?&tw=1&pmid=25710634 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25710634 #FOAvip English Wikipedia <ref>{{Cite pmid|25710634}}</ref> Toward a Biorelevant Structure of Protein Kinase C Bound Modulators: Design, Synthesis, and Evaluation of Labeled Bryostatin Analogs for Analysis with REDOR NMR Spectroscopy #MMPMID25710634 Loy BA; Lesser AB; Staveness D; Billingsley KL; Cegelski L; Wender PA J Am Chem Soc 2015[Mar]; 137 (10): 3678-85 PMID25710634show ga Protein kinase C (PKC) modulators are currently of great importance in preclinical and clinical studies directed at cancer, immunotherapy, HIV eradication, and Alzheimer?s disease. However, the bound conformation of PKC modulators in a membrane environment is not known. Rotational Echo Double Resonance (REDOR) NMR spectroscopy could uniquely address this challenge. However, REDOR NMR requires strategically-labeled, high affinity ligands to determine inter-label distances from which the conformation of the bound ligand in the PKC-ligand complex could be identified. Here we report the first computer-guided design and syntheses of three bryostatin analogs strategically-labeled for REDOR NMR analysis. Extensive computer analyses of energetically-accessible analog conformations suggested preferred labeling sites for the identification of the PKC-bound conformers. Significantly, three labeled analogs were synthesized, and, as required for REDOR analysis, all proved highly potent with PKC affinities (~1 nM) on par with bryostatin. These potent and strategically-labeled bryostatin analogs are new structural leads and provide the necessary starting point for projected efforts to determine the PKC-bound conformation of such analogs in a membrane environment, as needed to design new PKC modulators and understand PKC-ligand?membrane structure and dynamics. äToward a Biorelevant Structure of Protein Kinase C Bound Modulators: D(epmc).pdf DeepDyve Pubget Overpricing