structural insights into human peroxisome proliferator activated receptor delta (ppar-delta) selective ligand binding结构洞察人类过氧物酶体扩散者激活受体δ(ppar-delta)有选择性的配体结合.pdf

Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding 1. 1.¤ 1 1 Fernanda A. H. Batista , Daniela B. B. Trivella , Amanda Bernardes , Joyce Gratieri , 2 2 3 1 Paulo S. L. Oliveira , Ana Carolina M. Figueira , Paul Webb , Igor Polikarpov * ´ ˜ ˜ ˜ ´ ˆ 1 Instituto de Fısica de Sao Carlos, Universidade de Sao Paulo, Sao Carlos, Sao Paulo, Brazil, 2 Laboratorio Nacional de Biociencias, Centro Nacional de Pesquisas em ´ Energia e Materiais (CNPEM/ABTLUS) Laboratorio Nacional de Biociencias (LNBio), Campinas, Sao Paulo, Brazil, 3 Diabetes Center and Cancer Research Unit, The Methodist Hospital Research Institute, Houston, Texas, United States of America Abstract Peroxisome proliferator activated receptors (PPARs d, a and c) are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross- react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARd more tha