ArticleStructure (London, England : 1993)2025
Design of multi-target peptide modulators for protein chaperone networks.
Article in Structure (London, England : 1993), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- The Allosteric Revolution: From Static Structures to Conformational Ensembles and Next-Generation Therapeutics.Journal of molecular biology · 2026Review
- Post-Translational Modification as an Allosteric Switch in Hsp90: How Dual Phosphorylation Locks Chaperone Complexes into Hyperstabilized States.The journal of physical chemistry letters · 2026Article
- Article
- MOLECULE: Molecular-dynamics and Optimized deep Learning for Entropy-regularized Classification and Uncertainty-aware Ligand Evaluation.Journal of chemical theory and computation · 2025Article
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Authors and funding
28 authors.
Funding
Abstract
Essential chaperones heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90) collaborate in oncoprotein folding. Dual inhibition of these chaperones has shown synergy in preclinical studies but remains challenging to achieve. Using a computational approach, we designed peptides mimicking the predicted unfolding regions of Kinase CDK4, a client protein of both Hsp70 and Hsp90. Peptide Cdk4-2 is shown to simultaneously bind Hsp70, Hsp90, and co-chaperone Cdc37. Cdk4-2 is membrane permeable, inhibits CDK4-mediated retinoblastoma phosphorylation, and induces apoptosis in renal carcinoma cells. Structure-function studies identified a minimal pharmacophore for Hsp70 binding and critical interactions for peptide affinity. These findings demonstrate the feasibility of rationally designing multi-target modulators of chaperone networks. Cdk4-2 is a promising lead for therapeutic development, expanding the molecular space of modulators of cancer-associated multiprotein machineries. While focused on chaperones, the idea behind our strategy is general and immediately transferable to other multiprotein targets and networks.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.