Efficient Screening of α-Glucosidase Inhibitory Peptides From Seahorse Through the Innovative Joint Technique: De Novo Sequencing and Parallel SPOT Synthesis
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引用次数: 0
Abstract
In this research, de novo sequencing was innovatively combined with parallel SPOT synthesis for the efficient screening of biological peptides from TCM or seafood: seahorse with synergistic antioxidant and α-glucosidase inhibitory activities, which is promising for postprandial hyperglycemia management. Gastrointestinal digestion mimic and de novo sequencing were sequentially carried out to predict new peptides from seahorse. After bioinformatic analysis using Peptide Ranker, 82 peptides were eventually synthesized by efficient parallel SPOT technique, and Ser-Val-Try-Leu-Gly-Gly-Ser-Leu-Leu (SVWLGGSLL) was screened out as the most efficient peptide with synergistic antioxidant (DPPH radical scavenging activity of 77%) and α-glucosidase inhibitory activity (IC50 = 0.36 mM). Molecular docking was further carried out to illustrate the favorable ligand-receptor interactions formed such as hydrogen bonding and van der Waals force with low binding free energy of −7.8 kcal/mol. Moreover, pharmacokinetic analysis indicated that SVWLGGSLL was unrelated to toxicity with the advantage of gastrointestinal stability.
本研究创新性地将从头测序与平行SPOT合成相结合,从中药或海产海马中高效筛选具有协同抗氧化和α-葡萄糖苷酶抑制活性的生物多肽,有望用于餐后高血糖治疗。胃肠消化模拟和从头测序相继进行预测海马的新肽。利用Peptide Ranker进行生物信息学分析后,利用高效平行SPOT技术合成了82条多肽,筛选出ser - val - ry- leu - gly - gly - ser - leu - leu (SVWLGGSLL)为效率最高的多肽,具有协同抗氧化作用(清除DPPH自由基活性为77%)和α-葡萄糖苷酶抑制活性(IC50 = 0.36 mM)。进一步进行分子对接,以说明在−7.8 kcal/mol的低结合自由能下,形成了良好的配体-受体相互作用,如氢键和范德华力。此外,药代动力学分析表明,SVWLGGSLL与毒性无关,具有胃肠道稳定性的优势。
期刊介绍:
The official Journal of the European Peptide Society EPS
The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews.
The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.