Here's a Cathepsin K family of inhibitors with a straight ketone: Bioorganic & Medicinal Chemistry Letters Volume 17, Issue 1, 1 January 2007, Pages 22-27
and here's a structure paper (covalent adduct with the ketone) www.jbc.org/cgi/reprint/266/26/17695.pdf Here's a couple of Cruzain structures with ketone inhibitors. Look for ligands in the pdb called ZRA or ZYA http://www.rcsb.org/pdb/ligand/ligandsummary.do?hetId=ZYA http://www.rcsb.org/pdb/ligand/ligandsummary.do?hetId=ZRA Bioorg Med Chem. 2003 Jan 2;11(1):21-9. BACE (memapsin) and related enzymes are some of the most studied peptidase targets. I believe there were a few ketone inhibitors pulished for these enzymes, but I am honestly not sure if any of the structures are in the public domain. Here's an alcohol version of a peptidomimetic: http://www.jbc.org/cgi/content/full/277/7/4687 Here's a difluoro ketone one: Moore CL, Leatherwood DD, Diehl TS, Selkoe DJ, Wolfe MS. Difluoro Ketone Peptidomimetics Suggest a Large S1 Pocket for Alzheimer's gamma-Secretase: Implications for Inhibitor Design. J Med Chem. 2000 Sep 7;43(18):3434-3442. Michael adduct traps (alpha-unsaturated ketones) have been proposed for kinases with a Cys in the ATP site: http://www.freshpatents.com/Specific-kinase-inhibitors-dt20060413ptan20060079494.php Good luck, Artem > Hi all > > I have searched the PDB without much luck and wondered whether anyone out > there could confirm: > > I'm looking for co-crystal structures of enzymes with inhibitors that bind > to the catalytic group via a ketone moiety. Our case is a metalloprotease > with a ketomethylene peptide analogue but any kind will do. > > As far as I can tell, the PDB has a few examples with an aldehyde at one > of the termini of the inhibitor (e.g. 1LAN, 1CBX), and some with modified > ketones (e.g fluoro-, 1OD1, 1NJS) but none with an unmodified internal > ketone. > > So far, I've found some carboxypeptidase A papers from the 80's and > nothing since. Have I missed something? > > Sincerely > Jean Watermeyer > > > Jean Watermeyer > Division of Medical Biochemistry > IIDMM > University of Cape Town Health Sciences > Anzio Rd Observatory > 7925 > South Africa > > Tel. 021 4066832 > > > PLEASE UPDATE: my email address has changed: [EMAIL PROTECTED] > > Jean Watermeyer > Division of Medical Biochemistry > IIDMM > University of Cape Town Health Sciences > Anzio Rd Observatory > 7925 > South Africa > > Tel. 021 4066832 >
