title: Peptides inhibitory for the transcriptional regulatory function of human papillomavirus E2.
abstract: OBJECTIVE
  Human papillomavirus (HPV) infections are associated with cervical neoplasia. Cellular and viral proteins are known to interact with the papillomavirus E2 protein to initiate transcription and DNA replication in the HPV life cycle. Our aim was to identify peptides that bind to the HPV16 E2 protein and thereby inhibit its ability to alter the transcriptional activity of other genes.
  
  
  METHODS
  The HPV16 E2 protein was expressed and purified to near homogeneity in bacteria. We screened a phage display library of random peptides for ones that bound to HPV16 E2 protein. Among the isolated phage clones, we found that tryptophan-rich peptide sequences appeared repetitively in successive cycles of phage library panning. Replacement of the tryptophan amino acids in these dodecapeptides reduced the degree to which these peptides bound to the E2 protein. These E2-binding peptides were tested for their ability to inhibit the transcriptional regulatory function of E2 in a test cell line, which contained an E2 gene and a luciferase reporter gene driven by an E2-dependent transcriptional promoter.
  
  
  RESULTS
  Delivery of four of the E2 binding peptides into the intracellular compartment of the test cell line resulted in suppression of the E2-dependent luciferase expression. Deletion of the tryptophan residues from these peptides reduced their E2 binding and their ability to suppress E2-dependent luciferase expression in the test cell line.
  
  
  CONCLUSIONS
  These results suggest a strategy for the development of chemical inhibitors of E2-dependent transcription of viral genes in HPV-infected cells as an approach to the therapy of chronic HPV infections.
authors: Yale University, New Haven, Connecticut 06520, USA.
authors: Takuma
authors: T
authors: Fujii
authors: David
authors: D
authors: Austin
authors: David
authors: D
authors: Guo
authors: Srinivasan
authors: S
authors: Srimatkandada
authors: Tao
authors: T
authors: Wang
authors: Kaneyuki
authors: K
authors: Kubushiro
authors: Nobuo
authors: N
authors: Masumoto
authors: Katsumi
authors: K
authors: Tsukazaki
authors: Shiro
authors: S
authors: Nozawa
authors: Albert B
authors: AB
authors: Deisseroth
mesh_terms: D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000378:metabolism; D004268:DNA-Binding Proteins; D015967:Gene Expression Regulation, Viral; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D019151:Peptide Library; D014158:Transcription, Genetic / Q000187:drug effects*; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D019151:Peptide Library; D014764:Viral Proteins; D014364:Tryptophan; D008156:Luciferases