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Updated: Jul 4, 2026
Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Identification and characterization of topoisomerase II inhibitory peptides from soy protein hydrolysates
Wenyi Wang1, Sanjeewa G Rupasinghe, Mary A Schuler
1Department of Food Science and Human Nutrition and Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Abstract:
Topoisomerases are targets of several anticancer agents because their inhibition impedes the processes of cell proliferation and differentiation in carcinogenesis. With very limited information available on the inhibitory activities of peptides derived from dietary proteins, the objectives of this study were to employ co-immunoprecipitation to identify inhibitory peptides in soy protein hydrolysates in a single step and to investigate their molecular interactions with topoisomerase II. For this, soy protein isolates were subjected to simulated gastrointestinal digestion with pepsin and pancreatin, and the human topoisomerase II inhibitory peptides were co-immunoprecipitated and identified on a CapLC- Micromass Q-TOF Ultima API system. The inhibitory activity of these peptides from soy isolates toward topoisomerase II was confirmed using three synthetic peptides, FEITPEKNPQ, IETWNPNNKP,and VFDGEL, which have IC 50 values of 2.4, 4.0, and 7.9 mM, respectively. The molecular interactions of these peptides evaluated by molecular docking revealed interaction energies with the topoisomerase II C-terminal domain (CTD) (-186 to -398 kcal/mol) that were smaller than for the ATPase domain (-169 to -357 kcal/mol) and that correlated well with our experimental IC 50 values ( R (2) = 0.99). In conclusion, three peptides released from in vitro gastrointestinal enzyme digestion of soy proteins inhibited human topoisomerase II activity through binding to the active site of the CTD domain.
Insights
Soy peptides inhibit human topoisomerase II, a target for anticancer drugs. This study identified and characterized three soy-derived peptides that bind to topoisomerase II, offering potential for new cancer therapies.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Topoisomerases are crucial for cell proliferation and differentiation, making them key targets in cancer therapy.
- Limited research exists on the topoisomerase inhibitory potential of peptides from dietary proteins.
Purpose of the Study:
- To identify and characterize peptides from soy protein hydrolysates that inhibit human topoisomerase II.
- To investigate the molecular interactions between these peptides and topoisomerase II.
Main Methods:
- Soy protein isolates underwent simulated gastrointestinal digestion.
- Co-immunoprecipitation and CapLC-Micromass Q-TOF Ultima API were used for peptide identification.
- Molecular docking simulations assessed peptide-topoisomerase II interactions.
Main Results:
- Three soy-derived peptides (FEITPEKNPQ, IETWNPNNKP, VFDGEL) demonstrated inhibitory activity against topoisomerase II.
- These peptides exhibited IC50 values ranging from 2.4 to 7.9 mM.
- Molecular docking revealed stronger binding affinities to the topoisomerase II C-terminal domain (CTD) compared to the ATPase domain.
Conclusions:
- In vitro digestion of soy proteins releases peptides that inhibit human topoisomerase II activity.
- These peptides exert their inhibitory effects by binding to the active site of the CTD domain.
- The findings suggest potential applications of soy-derived peptides in developing novel anticancer agents targeting topoisomerase II.
