2c2m: Difference between revisions

[[Image:2c2m.gif|left|200px]]<br /><applet load="2c2m" size="350" color="white" frame="true" align="right" spinBox="true"  

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 10(6) M(-1) s(-1). The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH(2)-1-Naphth)(2) is the most potent compound and it inhibits caspase-3 with a k(2) 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.

2C2M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C2M OCA].  

[[Category: Asgian, J L.]]

[[Category: Campbell, A J.]]

[[Category: Ekici, O D.]]

[[Category: Gruetter, M G.]]

[[Category: James, K E.]]

[[Category: Li, Z Z.]]

[[Category: Powers, J C.]]

[[Category: Salvesen, G S.]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:44:10 2008''