sulfotyrosine recognition as marker for druggable sites in the extracellular spacesulfotyrosine识别作为制药网站在细胞外空间的标志.pdfVIP

Int. J. Mol. Sci. 2011, 12, 3740-3756; doi:10.3390/ijm OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article Sulfotyrosine Recognition as Marker for Druggable Sites in the Extracellular Space 1 1 2 1 Joshua J. Ziarek , Maxime S. Heroux , Christopher T. Veldkamp , Francis C. Peterson and Brian F. Volkman 1,* 1 Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; E-Mails: jziarek@ (J.J.Z.); mheroux@ (M.S.H.); fpeterso@ (F.C.P.) 2 Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA; E-Mail: veldkamc@ * Author to whom correspondence should be addressed; E-Mail: bvolkman@; Tel.: +1-414-955-8400; Fax: +1-414-955-6510. Received: 14 March 2011; in revised form: 16 May 2011 / Accepted: 23 May 2011 / Published: 8 June 2011 Abstract: Chemokine signaling is a well-known agent of autoimmune disease, HIV infection, and cancer. Drug discovery efforts for these signaling molecules have focused on developing inhibitors targeting their associated G protein-coupled receptors. Recently, we used a structure-based approach directed at the sulfotyrosine-binding pocket of the chemokine CXCL12, and thereby demonstrated that small molecule inhibitors acting up