Identification and characterization of topoisomerase II inhibitory peptides from soy protein hydrolysates.
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.
Wang
Wenyi
W
Department of Food Science and Human Nutrition and Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Rupasinghe
Sanjeewa G
SG
Schuler
Mary A
MA
Gonzalez de Mejia
Elvira
E
D000595:Amino Acid Sequence; D001665:Binding Sites; D004250:DNA Topoisomerases, Type II / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D047468:Immunoprecipitation; D008958:Models, Molecular; D010194:Pancreatin / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D010455:Peptides / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D030262:Soybean Proteins / Q000737:chemistry* / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D004791:Enzyme Inhibitors; D010455:Peptides; D030262:Soybean Proteins; D059005:Topoisomerase II Inhibitors; D010194:Pancreatin; D010434:Pepsin A; D004250:DNA Topoisomerases, Type II