Selective Neutral pH Inhibitor of Cathepsin B Designed Based on Cleavage Preferences at Cytosolic and Lysosomal pH Conditions

Cathepsin B is a cysteine protease that normally functions within acidic lysosomes for protein degradation, but in numerous human diseases, cathepsin B translocates to the cytosol having neutral pH where the enzyme activates inflammation and cell death. Cathepsin B is active at both the neutral pH 7...

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Veröffentlicht in:	ACS chemical biology 2021-09, Vol.16 (9), p.1628-1643
Hauptverfasser:	Yoon, Michael C, Solania, Angelo, Jiang, Zhenze, Christy, Mitchell P, Podvin, Sonia, Mosier, Charles, Lietz, Christopher B, Ito, Gen, Gerwick, William H, Wolan, Dennis W, Hook, Gregory, O’Donoghue, Anthony J, Hook, Vivian
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Sequence Binding Sites Cathepsin B - antagonists & inhibitors Cathepsins - metabolism Cell Membrane Permeability Cysteine Proteinase Inhibitors - chemistry Cysteine Proteinase Inhibitors - metabolism Cytosol - metabolism Endopeptidases - metabolism Humans Hydrogen-Ion Concentration Kinetics Lysosomes - metabolism Mass Spectrometry Peptides - chemistry Peptides - metabolism Protein Binding Substrate Specificity
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