685543-82-2

Upstream product

• 685543-77-5 trans-3-(benzylcarbamoyl)acrylic acid 
• 646532-79-8 tert-butyl (5S,8S,11S)-5–(2-(tert-butoxy)-2-oxoethyl)-8–(3-(tertbutoxy)-3-oxopropyl)-11-isopropyl-3,6,9,12-tetraoxo-1-phenyl-2-oxa-4,7,10,13,14-pentaazahexadecan-16-oate 
• 5292-43-3 bromoacetic acid tert-butyl ester 
• 100-46-9 benzylamine 
• 646532-71-0 tert-butyl (S)-4-((S)-2-(((benzyloxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanamido)-5-(((S)-1-hydrazinyl-3-methyl-1-oxobutan-2-yl)amino)-5-oxopentanoate 
• 474024-61-8 4-oxo-4-[(phenylmethyl)amino]-(E)-2-butenoic acid ethyl ester 

Relevant academic research and scientific papers

Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10

Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 106 M-1 s-1. The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH2-1-Naphth)2 is the most potent compound and it inhibits caspase-3 with a k2 value of 5620000 M-1 s-1. The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively. Aza-peptide Michael acceptors designed with caspase specific sequences are selective and do not show any cross reactivity with clan CA cysteine proteases such as papain, cathepsin B, and calpains. High-resolution crystal structures of caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors demonstrate the nucleophilic attack on C2 and provide insight into the selectivity and potency of the inhibitors with respect to the P1′ moiety.

Aza-Peptide Michael Acceptors: A New Class of Inhibitors Specific for Caspases and Other Clan CD Cysteine Proteases

Aza-peptide Michael acceptors are a new class of irreversible inhibitors that are highly potent and specific for clan CD cysteine proteases. The aza-Asp derivatives were specific for caspases, while aza-Asn derivatives were effective legumain inhibitors. Aza-Lys and aza-Orn derivatives were potent inhibitors of gingipain K and clostripain. Aza-peptide Michael acceptors showed no cross reactivity toward papain, cathepsin B, and calpain.