216489-70-2Relevant academic research and scientific papers
Use of papain as a model for the structure-based design of cathepsin K inhibitors: Crystal structures of two papain-inhibitor complexes demonstrate binding to S'-subsites
LaLonde, Judith M.,Zhao, Baoguang,Smith, Ward W.,Janson, Cheryl A.,DesJarlais, Renee L.,Tomaszek, Thaddeus A.,Carr, Thomas J.,Thompson, Scott K.,Oh, Hye-Ja,Yamashita, Dennis S.,Veber, Daniel F.,Abdel-Meguid, Sherin S.
, p. 4567 - 4576 (1998)
Papain has been used as a surrogate enzyme in a drug design effort to obtain potent and selective inhibitors of cathepsin K, a new member of the papain superfamily of cysteine proteases that is selectively and highly expressed in osteoclasts and is implic
Potent dipeptidylketone inhibitors of the cysteine protease cathepsin K
Marquis, Robert W.,Ru, Yu,Yamashita, Dennis S.,Oh, Hye-Ja,Yen, Jack,Thompson, Scott K.,Carr, Thomas J.,Levy, Mark A.,Tomaszek, Thaddeus A.,Ijames, Carl F.,Smith, Ward W.,Zhao, Baoguang,Janson, Cheryl A.,Abdel-Meguid, Sherin S.,D'Alessio, Karla J.,McQueney,Veber, Daniel F.
, p. 581 - 588 (2007/10/03)
Cathepsin K (EC 3.4.22.38) is a cysteine protease of the papain superfamily which is selectively expressed within the osteoclast. Several lines of evidence have pointed to the fact that this protease may play an important role in the degradation of the bone matrix. Potent and selective inhibitors of cathepsin K could be important therapeutic agents for the control of excessive bone resorption. Recently a series of peptide aldehydes have been shown to be potent inhibitors of cathepsin K. In an effort to design more selective and metabolically stable inhibitors of cathepsin K, a series of electronically attenuated alkoxymethylketones and thiomethylketones inhibitors have been synthesized. The X-ray co-crystal structure of one of these analogues in complex with cathepsin K shows the inhibitor binding in the primed side of the enzyme active site with a covalent interaction between the active site cysteine 25 and the carbonyl carbon of the inhibitor. Copyright (C) 1999 Elsevier Science Ltd.
