A Structure based Serological Test for Cervical Cancer

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DESCRIPTION (provided by applicant): The development of serological tests for high-risk human papillomavirus (HPV) infection, low-grade and high-grade squamous intraepithelial lesions and invasive cancer could play important roles in early detection, monitoring treatment and epidemiological studies. These conditions generate antibodies to HPV proteins providing a basis for serological assays. While both HPV peptides and recombinant proteins have been tested as antigens, various limitations have restricted their clinical usefulness. We have developed a method for constraining peptides to mimic the conformations of their cognate sequences in native proteins. These mimetics are enormously more reactive than peptides with antibodies generated by native proteins. They combine the convenience and stability of peptides with the sensititivies of native proteins. We propose to develop a set of constrained peptides from high-risk HPVs corresponding to conformational epitopes on the L1 capsid protein, the E2 transcription control protein and the E6 and E7 oncoproteins and assess their potentials for use in a serological assay.