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10.1002/anie.202008665 http://scihub22266oqcxt.onion/10.1002/anie.202008665 32757352!7436718!32757352     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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\32757352.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Angew+Chem+Int+Ed+Engl 2020 ; 59 (45): 20154-20160 Nephropedia Template TP {{tp|p=32757352|t=2020. The Enzyme-Free Release of Nucleotides from Phosphoramidates Depends Strongly on the Amino Acid |pdf=|usr=}}{{32757352}} gab.com Text The Enzyme-Free Release of Nucleotides from Phosphoramidates Depends Strongly on the Amino Acid JO: Angew Chem Int Ed Engl http://www.kidney.de/pget.php?&tw=1&pmid=32757352 #FOAvip Phosphoramidates composed of an amino acid and a nucleotide analogue are critical metabolites of prodrugs, such as remdesivir. Hydrolysis of the phosphoramidate liberates the nucleotide, which can then be phosphorylated to become the pharmacologically active triphosphate. Enzymatic hydrolysis has been demonstrated, but a spontaneous chemical process may also occur. We measured the rate of enzyme-free hydrolysis for 17 phosphoramidates of ribonucleotides with amino acids or related compounds at pH 7.5. Phosphoramidates of proline hydrolyzed fast, with a half-life time as short as 2.4 h for Pro-AMP in ethylimidazole-containing buffer at 37 degrees C; 45-fold faster than Ala-AMP and 120-fold faster than Phe-AMP. Crystal structures of Gly-AMP, Pro-AMP, betaPro-AMP and Phe-AMP bound to RNase A as crystallization chaperone showed how well the carboxylate is poised to attack the phosphoramidate, helping to explain this reactivity. Our results are significant for the design of new antiviral prodrugs. Twit Text FOAVip The Enzyme-Free Release of Nucleotides from Phosphoramidates Depends Strongly on the Amino Acid ????Angew Chem Int Ed Engl http://www.kidney.de/pget.php?&tw=1&pmid=32757352 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32757352 #FOAvip English Wikipedia <ref>{{Cite pmid|32757352}}</ref> The Enzyme-Free Release of Nucleotides from Phosphoramidates Depends Strongly on the Amino Acid #MMPMID32757352 Jovanovic D; Tremmel P; Pallan PS; Egli M; Richert C Angew Chem Int Ed Engl 2020[Nov]; 59 (45): 20154-20160 PMID32757352show ga Phosphoramidates composed of an amino acid and a nucleotide analogue are critical metabolites of prodrugs, such as remdesivir. Hydrolysis of the phosphoramidate liberates the nucleotide, which can then be phosphorylated to become the pharmacologically active triphosphate. Enzymatic hydrolysis has been demonstrated, but a spontaneous chemical process may also occur. We measured the rate of enzyme-free hydrolysis for 17 phosphoramidates of ribonucleotides with amino acids or related compounds at pH 7.5. Phosphoramidates of proline hydrolyzed fast, with a half-life time as short as 2.4 h for Pro-AMP in ethylimidazole-containing buffer at 37 degrees C; 45-fold faster than Ala-AMP and 120-fold faster than Phe-AMP. Crystal structures of Gly-AMP, Pro-AMP, betaPro-AMP and Phe-AMP bound to RNase A as crystallization chaperone showed how well the carboxylate is poised to attack the phosphoramidate, helping to explain this reactivity. Our results are significant for the design of new antiviral prodrugs. |Adenosine Monophosphate/analogs & derivatives/chemistry/metabolism[MESH] |Alanine/analogs & derivatives/chemistry/metabolism[MESH] |Amides/chemistry/*metabolism[MESH] |Amino Acids/*chemistry[MESH] |Antiviral Agents/chemistry/metabolism/pharmacology[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/pathology/virology[MESH] |Catalytic Domain[MESH] |Crystallography, X-Ray[MESH] |Half-Life[MESH] |Hydrogen-Ion Concentration[MESH] |Hydrolysis[MESH] |Kinetics[MESH] |Molecular Dynamics Simulation[MESH] |Nucleotides/chemistry/*metabolism[MESH] |Phosphoric Acids/chemistry/*metabolism[MESH] |Ribonuclease, Pancreatic/chemistry/metabolism[MESH]The Enzyme-Free Release of Nucleotides from Phosphoramidates Depends S(epmc).pdf DeepDyve Pubget Overpricing