title: Design of peptides as inhibitors of human papillomavirus 16 transcriptional regulator E1-E2.
abstract: Human papillomavirus 16 (HPV 16) is a DNA virus that is capable of infecting humans and causing cervical cancer. HPV16 E2 plays an important role in viral gene regulation. This work aims to predict the binding conformations and interactions between the dodecapeptides and HPV16 E2 as well as to design novel peptide inhibitors that are capable of binding to HPV16 E2 and disrupt the transcriptional regulator E1-E2 complex formation, using computational protein design techniques. Based on previously reported peptide4 (TWFWPYPYPHLP), novel peptide inhibitors were designed and five peptides that showed lower binding energy to HPV16 E2 than that of peptide4, were selected for in vitro experiments. Enzyme-linked immunosorbent (ELISA) assay showed that Y6R, W4H_Y6R, and W4H peptides bound to HPV16 E2 with higher affinity than peptide4 did. Moreover, Y6R, W4H_Y6R, and W4H peptides more effectively inhibited E1-E2 complex formation than peptide4. This work revealed important interactions between the peptides and E1-E2 complex, suggesting a strategy for development of more potent peptide inhibitors.
authors.affiliation: Structural and Computational Biology Research Group, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Worrapon
authors.initials: W
authors.lastname: Kantang
authors.affiliation: Structural and Computational Biology Research Group, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Surasak
authors.initials: S
authors.lastname: Chunsrivirot
authors.affiliation: Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Nongnuj
authors.initials: N
authors.lastname: Muangsin
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.affiliation: Structural and Computational Biology Research Group, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. kuakarun.k@chula.ac.th.
authors.forename: Kuakarun
authors.initials: K
authors.lastname: Krusong
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001681:Biological Assay; D015195:Drug Design; D052162:Human papillomavirus 16 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D015514:Oncogene Proteins, Fusion; D010455:Peptides; D014764:Viral Proteins; C072777:oncogene protein E1--E4, Human papillomavirus type 16
keywords: ClusPro; E1; E2; HPV16; I-TASSER; docking; small peptide inhibitor