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Design of peptides as inhibitors of human papillomavirus 16 transcriptional regulator E 1– E 2
Author(s) -
Kantang Worrapon,
Chunsrivirot Surasak,
Muangsin gnuj,
Poovorawan Yong,
Krusong Kuakarun
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12790
Subject(s) - peptide , regulator , human papillomavirus , in vitro , negative regulator , chemistry , gene , transcriptional regulation , microbiology and biotechnology , biology , biochemistry , computational biology , gene expression , medicine
Human papillomavirus 16 ( HPV 16) is a DNA virus that is capable of infecting humans and causing cervical cancer. HPV 16 E 2 plays an important role in viral gene regulation. This work aims to predict the binding conformations and interactions between the dodecapeptides and HPV 16 E 2 as well as to design novel peptide inhibitors that are capable of binding to HPV 16 E 2 and disrupt the transcriptional regulator E 1– E 2 complex formation, using computational protein design techniques. Based on previously reported peptide4 ( TWF W P Y PYPHLP ), novel peptide inhibitors were designed and five peptides that showed lower binding energy to HPV 16 E 2 than that of peptide4, were selected for in vitro experiments. Enzyme‐linked immunosorbent ( ELISA ) assay showed that Y 6 R , W 4 H _ Y 6 R , and W 4 H peptides bound to HPV 16 E 2 with higher affinity than peptide4 did. Moreover, Y 6 R , W 4 H _ Y 6 R , and W 4 H peptides more effectively inhibited E 1– E 2 complex formation than peptide4. This work revealed important interactions between the peptides and E 1– E 2 complex, suggesting a strategy for development of more potent peptide inhibitors.