Efficient Screening of α-Glucosidase Inhibitory Peptides From Seahorse Through the Innovative Joint Technique: De Novo Sequencing and Parallel SPOT Synthesis

peer-reviewed · Journal of Peptide Science · 2025

peer-reviewed · Journal of Peptide Science · 2025. Shengfang Gao et al. In this research, de novo sequencing was innovatively combined with parallel SPOT synthesis for the efficient…
Date 2025-06-01
Type peer-reviewed
Venue Journal of Peptide Science
Publisher Wiley
Contribution downstream-application
DOI 10.1002/psc.70023
Citations (OpenAlex) 1

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 (IC 50 = 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.

Authors

  1. Shengfang Gao · Beijing University of Chinese Medicine
  2. Yimeng Li · Beijing University of Chinese Medicine
  3. Xiaohui Zhang · Beijing University of Chinese Medicine
  4. Zhuo Cao · Beijing University of Chinese Medicine
  5. Youyou Guo · Beijing University of Chinese Medicine
  6. Runkun Zhao · Beijing University of Chinese Medicine
  7. Lifan Li · Beijing University of Chinese Medicine
  8. Hongying Lin · Beijing University of Chinese Medicine
  9. Qi Qin · Capital Medical University, Xuan Wu Hospital of the Capital Medical University
  10. Bingqing Yi · Beijing University of Chinese Medicine
  11. Guodong Zhao · Beijing University of Chinese Medicine

Methods and tools

  • Parallel synthesis + de novo peptide screening: Joint technique pairing de novo sequencing of a simulated-digestion hydrolysate with parallel peptide synthesis, so each predicted sequence is synthesised, screened for activity and checked against the standard’s retention time and MS/MS spectrum. Applied to sea cucumber and seahorse.

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