5-Benzamido-pyrimidone/pyrimidine-2-methylcarboxylates monomeric building blocks for alpha-helix mimetics targeting HSP90
Monomeric building blocks that can be combined via peptide synthesis into dimeric or trimeric structures to mimic hot spot regions and amino acid side chains of HSP90, enabling inhibition of its dimerization process for potential therapeutic applications.
Overview
This research introduces monomeric building blocks based on 5-benzamido-pyrimidone and pyrimidine-2-methylcarboxylate scaffolds designed to serve as alpha-helix mimetics targeting heat shock protein 90 (HSP90). The building blocks can be combined through peptide synthesis into dimeric or trimeric structures that replicate specific hot spot regions and amino acid side chains involved in HSP90 dimerization. By mimicking these critical protein-protein interaction interfaces, the constructs offer a route to disrupting HSP90 dimerization, a process relevant to cancer and other diseases where HSP90 chaperone activity plays a role.
Technical specifications
- Core chemistry: 5-benzamido-pyrimidone and pyrimidine-2-methylcarboxylate scaffolds functioning as monomeric building blocks
- Assembly strategy: Peptide synthesis enabling dimeric and trimeric combinations to match hot spot regions of HSP90
- Mechanism of action: Alpha-helix mimicry of amino acid side chains at the dimerization interface to inhibit HSP90 dimerization
- Design rationale: Targeted replication of specific hot spot residues rather than broad-spectrum binding
- Modularity: Flexible oligomerization (di- vs. trimers) to tune affinity and selectivity profiles
Technology readiness level
The work is at an early-stage research phase. The monomeric building blocks have been defined and the peptide synthesis route for assembling dimeric and trimeric alpha-helix mimetics has been proposed. Future validation will focus on confirming that the assembled constructs effectively mimic the targeted hot spot regions and inhibit HSP90 dimerization in biochemical and cellular assays.
About Heinrich Heine Universität Düsseldorf
Heinrich Heine Universität Düsseldorf is a comprehensive public research university anchored by a major medical faculty and a modern science campus. An integrated university hospital and shared core facilities enable clinical translation and access to specialized instrumentation for joint studies. Companies collaborate through on‑campus spaces, contract research, and tailored partnership models, with quick reach to suppliers and manufacturing across North Rhine‑Westphalia’s Rhine‑Ruhr corridor. Research is supported by competitive funding from the German Research Foundation and federal and state ministries, alongside European Union programs. A dedicated technology transfer office manages IP, licensing, and startup support to accelerate industry uptake.
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