Structure-Based Stepwise Screening of PPARγ Antagonists as Potential Competitors with NCOA1 Coactivator Peptide for PPARγ CIS Site

Shen, Yi; Chi, Hongbo; Zhou, Jinhu; Luo, Le; Tao, Qian; Qi, Cancan; Gao, Zu–Hua

doi:10.1007/s10989-018-9782-x

Cited by 8 publications

(1 citation statement)

References 44 publications

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“…As shown in Figure 4, the C‐terminal helix 12 (H12) of PPARγ is highly mobile and can switch between different states to control the PMI binding and unbinding by creating and destroying the coactivator‐binding site (CBS) on PPARγ surface, respectively. Different allosteric regulators, including agonist, antagonist, and inverse agonist, can target a common ligand‐binding site (LBS) in the interior of PPARγ protein, where is not overlapped with CBS but spatially vicinal to H12, thus modulating the PPARγ transition between different states of activation, basal and inactivation by stabilizing or destabilizing PMI through regulating the H12 in different locations [86, 87].…”

Section: Targeting Pmis With Chemical Drugs and Protein Agentsmentioning

confidence: 99%

Targeting peptide‐mediated interactions in omics

et al. 2022

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Peptide-mediated interactions (PMIs) play a crucial role in cell signaling network, which are responsible for about half of cellular protein-protein associations in the human interactome and have recently been recognized as a new kind of promising druggable target for drug development and disease therapy. In this article, we give a systematic review regarding the proteome-wide discovery of PMIs and targeting druggable PMIs (dPMIs) with chemical drugs, self-inhibitory peptides (SIPs) and protein agents, particularly focusing on their implications and applications for therapeutic purpose in omics. We also introduce computational peptidology strategies used to model, analyze, and design PMI-targeted molecular entities and further extend the concepts of protein context, direct/indirect readout, and enthalpy/entropy effect involved in PMIs. Current issues and future perspective on this topic are discussed. There is still a long way to go before establishment of efficient therapeutic strategies to target PMIs on the omics scale.

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Section: Targeting Pmis With Chemical Drugs and Protein Agentsmentioning

confidence: 99%