Efficient Screening of Synergistic Antioxidant and AChE Inhibitory Peptides From Sea Cucumber (Stichopus japonicus) Using a Novel Approach Combining De Novo Sequencing and Parallel Peptide Synthesis
机构：[1]Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China[2]Beijing Univ Chinese Med, Qi Huang Chinese Med Sch, Beijing, Peoples R China[3]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing, Peoples R China首都医科大学宣武医院[4]Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, Beijing, Peoples R China首都医科大学宣武医院[5]Minist Educ, Engn Res Ctr Pharmaceut Chinese Mat Med & New Drug, Beijing, Peoples R China
In this study, we report for the first time that de novo sequencing can be combined with parallel peptide synthesis to facilitate high-throughput activity screening of biological peptides from natural food. Sea cucumber (Stichopus japonicus) intestine was utilized as an example, undergoing gastrointestinal digestion followed by de novo sequencing to predict potential peptide sequences. These peptides were efficiently synthesized for the first time using a readily accessible filter pipette tip as parallel reaction vessels, eliminating the use of any expensive equipment. This method enabled the synthesis of numerous peptides at a milligram scale with microfluidic amino acid flowing through the solid resin. After high-throughput activity screening, peptide LSPGV was shown to exhibit the most potent antioxidant activity (DPPH radical scavenging activity [DRSA]: 88.96%) and strongest acetylcholinesterase (AChE) inhibition (IC50 of 7.32 mu M) simultaneously. The reduction in paralysis, amyloid-beta (A beta) aggregation, and AChE activity in vivo was further confirmed in an animal model, Caenorhabditis elegans. 3D structure simulation and molecular docking study were also conducted for LSPGV to illustrate its potential conformation and favorable binding interactions with AChE. As a candidate for Alzheimer's disease (AD) treatment, LSPGV significantly enhances the value of sea cucumber intestine by-products.
基金：
National Natural Science Foundation of China; Beijing Natural Science Foundation [2232028]; Beijing Nova Program [20240484566]; Student Scientific Research Project of Beijing University of Chinese Medicine [XBB24026]; Research Subject of Educational Science of Beijing University of Chinese Medicine [XJY23016]; [22301018]
第一作者机构：[1]Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China
通讯作者：
通讯机构：[1]Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China[5]Minist Educ, Engn Res Ctr Pharmaceut Chinese Mat Med & New Drug, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Li Yimeng,Gao Shengfang,Zhang Xiaohui,et al.Efficient Screening of Synergistic Antioxidant and AChE Inhibitory Peptides From Sea Cucumber (Stichopus japonicus) Using a Novel Approach Combining De Novo Sequencing and Parallel Peptide Synthesis[J].PEPTIDE SCIENCE.2025,117(3):doi:10.1002/pep2.70002.
APA：
Li, Yimeng,Gao, Shengfang,Zhang, Xiaohui,Cao, Zhuo,Guo, Youyou...&Zhao, Guodong.(2025).Efficient Screening of Synergistic Antioxidant and AChE Inhibitory Peptides From Sea Cucumber (Stichopus japonicus) Using a Novel Approach Combining De Novo Sequencing and Parallel Peptide Synthesis.PEPTIDE SCIENCE,117,(3)
MLA：
Li, Yimeng,et al."Efficient Screening of Synergistic Antioxidant and AChE Inhibitory Peptides From Sea Cucumber (Stichopus japonicus) Using a Novel Approach Combining De Novo Sequencing and Parallel Peptide Synthesis".PEPTIDE SCIENCE 117..3(2025)
