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COMPARATIVE ANALYSIS OF LIGAND BINDING MODES OF PPAR-γ FULL AND PARTIAL AGONISTS

Clinically used thiazolidinediones such as rosiglitazone and pioglitazone control hyperglycemia by acting as full agonist on PPARγ receptors. Unfortunately, they suffer with serious side effects such as weight gain, fluid retention, congestive heart failure, bladder cancer etc. It is reported that, these effects are attributed to full activation of PPARγ receptors by these ligands. Newer approaches like development and selective PPAR modulators or partial agonists have been extensively researched to overcome or reduce these side-effects. In this research paper, we have carried out a comparative analysis of binding agonists. The results show that PPARγ full agonists form H-bond interactions with TYR473, His 449, His 323 whereas partial agonists form H-bond interaction with Ser 342, Ser 289 and Arg 280. The above findings, therefore, may help in choosing PPAR-γ leads with partial agonistic activity.