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10.1021/acs.jmedchem.1c00628 http://scihub22266oqcxt.onion/10.1021/acs.jmedchem.1c00628 34288674!10504874!34288674     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Med+Chem 2021 ; 64 (15): 11267-11287 Nephropedia Template TP {{tp|p=34288674|t=2021. Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases |pdf=|usr=}}{{34288674}} gab.com Text Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases JO: J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=34288674 #FOAvip Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease-Trypanosoma cruzi. These SMAIs exerted potent, reversible inhibition of cruzain (K(i)* = 18-350 nM) while apparently protecting the free aldehyde in cell-based assays. We synthesized prodrugs of the SMAIs that could potentially improve their pharmacokinetic properties. We also elucidated the kinetic and chemical mechanism of SMAIs and applied this strategy to the design of anti-SARS-CoV-2 inhibitors. Twit Text FOAVip Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases ????J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=34288674 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34288674 #FOAvip English Wikipedia <ref>{{Cite pmid|34288674}}</ref> Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases #MMPMID34288674 Li L; Chenna BC; Yang KS; Cole TR; Goodall ZT; Giardini M; Moghadamchargari Z; Hernandez EA; Gomez J; Calvet CM; Bernatchez JA; Mellott DM; Zhu J; Rademacher A; Thomas D; Blankenship LR; Drelich A; Laganowsky A; Tseng CK; Liu WR; Wand AJ; Cruz-Reyes J; Siqueira-Neto JL; Meek TD J Med Chem 2021[Aug]; 64 (15): 11267-11287 PMID34288674show ga Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease-Trypanosoma cruzi. These SMAIs exerted potent, reversible inhibition of cruzain (K(i)* = 18-350 nM) while apparently protecting the free aldehyde in cell-based assays. We synthesized prodrugs of the SMAIs that could potentially improve their pharmacokinetic properties. We also elucidated the kinetic and chemical mechanism of SMAIs and applied this strategy to the design of anti-SARS-CoV-2 inhibitors. |*COVID-19 Drug Treatment[MESH] |Aldehydes/*chemistry/metabolism/pharmacology[MESH] |Cathepsin L/antagonists & inhibitors/metabolism[MESH] |Chagas Disease/*drug therapy[MESH] |Cysteine Endopeptidases/metabolism[MESH] |Cysteine Proteases/metabolism[MESH] |Cysteine Proteinase Inhibitors/chemistry/*therapeutic use[MESH] |Drug Design[MESH] |Humans[MESH] |Kinetics[MESH] |Models, Molecular[MESH] |Molecular Structure[MESH] |Protozoan Proteins/antagonists & inhibitors/metabolism[MESH] |SARS-CoV-2/drug effects/*enzymology[MESH] |Structure-Activity Relationship[MESH]Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cyste(epmc).pdf DeepDyve Pubget Overpricing