Map205-based peptidomimetic inhibitors of the polo-box domain of polo-like kinase 1
Thursday, September 17, 2015 — Poster Session II
- J Jang
- DT Hymel
- TR Burke
Polo-like kinase 1 (Plk1) is an integral kinase in the cell cycle. Its structure consists of a kinase domain at the N-terminus, as well as two highly conserved polo-box domains (PBD) located near the C-terminus, which are involved in cellular localization and regulation of kinase activity. Plk1 regulates the initiation of mitosis by activating key proteins that are involved in centrosome maturation and spindle fiber assembly. However, it is known that certain types of cancers rely heavily on Plk1 overexpression for their growth and proliferation. As a result, Plk1 has become a meritable and relevant target for peptide-based drugs. Current peptides being researched are able to bind to the highly conserved polo-box domain of Plk1 with low nanomolar potency; however, these drugs contain a critical phosphothreonine residue that impedes the ability of these peptides to cross the cell membrane. Therefore, this study aims to synthesize and evaluate peptidomimetics of 205kDa microtubule-associated protein (Map205), which is a Drosophila protein that has been co-crystallized with the polo-box domain of zebrafish Plk1. Analogs of Map205 are hypothesized to bind to the polo-box domain without a phosphothreonine residue, which could potentially lead to a peptidomimetic that can permeate cell membranes, inhibit Plk1, and halt mitosis in cancerous cells.
Category: Chemical Biology