An alpha helix conformationally restricted peptide is recognized by cervical carcinoma patients' sera

J Med Chem. 2003 Dec 4;46(25):5389-94. doi: 10.1021/jm030210x.

Abstract

Human papillomavirus type 16 (HPV-16) represents the major cervical carcinoma associated virus among women, especially in Colombia. It has thus become important to develop reliable inexpensive tests for detecting the presence of this virus. It has been shown that HPV16-E7 oncoprotein structural features have three alpha-helical structures and a loop-like structure. The hydrazone link approach was used to mimic helix secondary substructures. Sera from women with invasive cervical carcinoma were tested against conformationally restricted peptides and their respective linear peptides to identify conformational epitopes. One peptide that was conformationally restricted to an alpha-helix showed very strong positive reaction with sera from women having invasive cervical carcinoma; there was no reaction with sera from patients with other carcinomas, children, or healthy women. NMR studies confirmed this peptide's alpha-helical structure. The observation that constrained protein substructure peptidomimetics can identify new conformationally sensitive antibodies in cervical carcinoma patients' sera is very important, since these antibodies are almost all generated by native proteins, providing a new selection of antibodies for diagnostic and vaccine studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hydrazones / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Mimicry
  • Oncogene Proteins, Viral / chemistry*
  • Papillomavirus E7 Proteins
  • Peptides / chemistry*
  • Protein Structure, Secondary
  • Serologic Tests / methods
  • Serum
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / diagnosis*

Substances

  • Hydrazones
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Peptides
  • oncogene protein E7, Human papillomavirus type 16