研究揭示DNA编码环肽库中不同环化方法对筛选结果的影响

Core Insights - The article discusses advancements in the field of cyclic peptide libraries, particularly focusing on the DNA-encoded library technology (DELT) which enhances the screening and discovery of novel cyclic peptides with superior properties [1][2]. Group 1: Technology and Methodology - DELT allows for the rapid construction and screening of large compound libraries by linking specific nucleic acid tags to peptide molecules, providing an efficient and cost-effective platform for high-throughput screening of cyclic peptides [1]. - Researchers designed and synthesized eight cyclic peptide sub-libraries, collectively forming a super library containing approximately 100 million different cyclic peptide molecules, utilizing various cyclization methods [2]. Group 2: Research Findings - In screening for the tumor-related protein MDM2, multiple sub-libraries exhibited a consistent enrichment pattern, with specific amino acid sequences showing high binding affinity, achieving a maximum binding activity (Ki) of 11 nM [2]. - The study revealed that some cyclic peptide combinations, which had low enrichment in single sub-libraries, demonstrated good activity after off-DNA synthesis, indicating that single sub-library screening may underestimate the potential of high-activity molecules [2]. Group 3: Specific Case Studies - For the GIT1 screening, no consistent enrichment pattern was observed across different sub-libraries, leading to the identification of two cyclic peptide compounds, one of which effectively blocked the interaction with β-PIX [3]. - The research emphasized the importance of using multiple methods, such as competitive screening and in vitro experiments, to comprehensively validate the authenticity and specificity of the screened compounds [3]. Group 4: Publication and Support - The research findings were published in JACS Au under the title "Influence of Macrocyclization Strategies on DNA-Encoded Cyclic Peptide Libraries," and the work received support from the National Natural Science Foundation of China [3].