New human papilloma virus E2 transcription factor mimics: a tripyrrole-peptide conjugate with tight and specific DNA-recognition

MARIA JULIETA COMIN*; DIANA E. WETZLER*; MARIANA GALLO

PLOS ONE

PUBLIC LIBRARY SCIENCE

Año: 2011 vol. 6 p. 22409 - 22410

1932-6203

Human papillomavirus (HPV) is the main causative agent of cervical cancer, particularly high risk strains such us HPV-16, -18 and -31. The viral encoded E2 protein acts as a transcriptional modulator and exerts a key role in viral DNA replication. Thus, E2 constitutes an attractive target for developing antiviral agents. E2 is a homodimeric protein that interacts with the DNA target through an α-helix of each monomer. However, a peptide corresponding to the DNA recognition helix of HPV-16 E2 binds DNA with lower affinity than its full-length DNA binding domain. Therefore, in an attempt to promote the DNA binding of the isolated peptide, we have designed a conjugate compound of the E2 α-helix peptide and a derivative of the antibiotic distamycin, which involves simultaneous minor- and major-groove interactions.