Abstract

In previous scientific efforts random peptide libraries containing millions of 90 Mm TentaGel beads, each withits own unique ovarian cancer disease associated amino acid sequence were generated by using ‘‘one-bead one-compound’’ combinatorial chemistry tchnology. A cyclic random 8-mer library was screened with CAOV-3 (a human ovarian adenocarcinoma cell line) and beads with a unique ligandthat bind to the cell surface receptors were coated byone or more layers of cells. These positive beads were isolated, stripped, and microsequenced. Several peptidemotifs were identified from these screenings, some of which were novel and unique, e.g., cDGX4GX6X7c. Structure-activity relationship studies of this peptiderevealed that the L-aspartate residue at position 2, thetwo glycines at positions 3 and 5, and the two Dcysteinesat the amino and COOH terminus are critical foractivity. Here, in Biogenea we have for the first time in silico discovered novel targeting peptide chemical pharmacophore for human ovarian cancer highly expressed mRNAs fro ‘‘one-bead one-compound’’combinatorial libraries.

Keywords

hydrophobic; residue;computer-aided; discovery;novel targeting; peptide;chemical; pharmacophore;human ovarian cancer; highly expressed; mRNAs, ‘‘one-bead one-compound’’combinatorial libraries;