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Extra info for Drug Discovery Strategies and Methods
Cambridge: Royal Society of Chemistry, 1989:182–196. Rotstein SH, Murcko MA. GroupBuild: a fragment-based method for de novo drug design. J Med Chem 1993; 36:1700–1710. Stallings WC, Abdel-Meguid SS, Lim LW, Shieh H-S, Dayringer HE, Leimgruber NK, Stegeman RA, Anderson KS, Sikorski JA, Padgette SR, Kishore GM. Structure and topological symmetry of the glyphosphate 5-enol-pyruvylshikimate-3-phosphate synthase: a distinctive protein fold. Proc Natl Acad Sci USA 1991; 88:5046–5050. Cunninghum BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA.
From Ref. ) 30 Metcalf and Sawyer formation of bone) as shown by enhanced bone formation and osteoblast diﬀerentiation rates in Src (–/–) mice . Together, these data provide complementary, mechanistic evidence to validate Src as a viable therapeutic target for the treatment of bone diseases such as osteoporosis. III. SH2 DOMAINS AND PHOSPHOPEPTIDE BINDING The question of whether ligand binding speciﬁcity exists among SH2 domains was addressed, quite elegantly, by Cantley et al. [6,9], who used synthesized combinatorial libraries of pTyr-containing peptides.
J Med Chem 1998; 41:4567–4576. Thompson SK, Smith WW, Zhao B, Halbert SM, Tomaszek TA, Tew DG, Levy MA, Janson CA, DAlessio KJ, McQueney MS, Kurdyla J, Jones CS, DesJarlais RL, Abdel-Meguid SS, Veber DF. Structure-based design of cathepsin K inhibitors containing a benzyloxy-substituted benzoyl peptidomimetic. J Med Chem 1998; 41:3923–3927. 2 Src Homology-2 Domains and Structure-Based, Small-Molecule Library Approaches to Drug Discovery Chester A. A. The elucidation of cell-receptor-associated signal transduction pathways by means of the tools of biochemistry and molecular genetics has resulted in the identiﬁcation of a multitude of protein targets for therapeutic intervention (Table 1) .