A one-step, resin-compatible Cys-Trp cross-linking system opens a new avenue for stapled peptide therapeutics.
2/5 보강
OpenAlex 토픽 ·
Chemical Synthesis and Analysis
Click Chemistry and Applications
Sulfur-Based Synthesis Techniques
Protein-protein interactions (PPIs) are attractive yet challenging drug targets, motivating the development of conformationally constrained peptides such as stapled α-helices.
APA
Masaya Denda, Yutaka Kohmura, et al. (2026). A one-step, resin-compatible Cys-Trp cross-linking system opens a new avenue for stapled peptide therapeutics.. Bioorganic & medicinal chemistry, 137, 118622. https://doi.org/10.1016/j.bmc.2026.118622
MLA
Masaya Denda, et al.. "A one-step, resin-compatible Cys-Trp cross-linking system opens a new avenue for stapled peptide therapeutics.." Bioorganic & medicinal chemistry, vol. 137, 2026, pp. 118622.
PMID
41818855 ↗
Abstract 한글 요약
Protein-protein interactions (PPIs) are attractive yet challenging drug targets, motivating the development of conformationally constrained peptides such as stapled α-helices. Here we report a one-pot cysteine-tryptophan (Cys-Trp) cross-linking strategy that enables direct formation of Trp-indole CH sulfenylation staples concomitant with global side-chain deprotection and resin cleavage. Application of this approach afforded a Cys-Trp-stapled analogue of estrogen receptor-α (ERα) activity regulator synthetic peptide (ERAP), designed to disrupt a pathogenic PPI implicated in breast cancer. The resulting stapled ERAP, stERAP(C-W), exhibited potent and sustained antiproliferative activity comparable to that of the original stERAP. Moreover, stereochemical modification at the stapling residues was readily achieved, and circular dichroism (CD) analyses revealed a systematic decrease in α-helicity upon D-amino acid substitution. Overall, this study establishes Cys-Trp stapling as a concise and versatile platform for generating bioactive stapled peptides with tunable conformational properties.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- Cysteine
- Tryptophan
- Peptides
- Cross-Linking Reagents
- Cell Proliferation
- Structure-Activity Relationship
- Antineoplastic Agents
- Estrogen Receptor alpha
- Molecular Structure
- Cell Line
- Tumor
- Dose-Response Relationship
- Drug
- Breast cancer therapeutics
- CH sulfenylation of indole
- Cysteine–tryptophane cross-linking
- S-protected cysteine sulfoxide
- Stapled-peptide
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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