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Synthesis of a novel cyclic peptide-drug conjugate targeting CDCP1 for non-small cell lung cancer therapy

CSEF · 2023 Chemistry First Award

Dinker Arushi · 11

Overview

Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer deaths. Many chemotherapeutic agents non-specifically target dividing cells, thus requiring a higher dosage to achieve therapeutic success. However, high-dose chemotherapy can induce cell death in healthy tissues, leading to undesirable side effects. One approach to achieving a sufficient therapeutic effect with a lower dose of chemotherapy is to engineer a peptide-drug conjugate (PDC) that targets cancer cells specifically. PDCs target cancer cells by binding to a biomarker specific to that cancer and delivering a cytotoxic payload. To identify a biomarker for NSCLC, I examined gene expression data from the Cancer Genome Atlas. I observed that the CSMD3 gene, which encodes CDCP1, was overexpressed in 39.1% of NSCLC cells. CDCP1 is a transmembrane protein involved in anoikis, a form of cell death triggered by the loss of matrix attachment. Resistance to anoikis may be required for cancer cells to undergo metastasis. CDCP1 therefore represents a promising target for anti-metastatic therapy. Cyclic peptides have beneficial properties for PDC design including increased binding affinity, better membrane permeability, and resistance to hydrolysis. To design a peptide-drug conjugate (PDC) that targets CDCP1, I used molecular modeling and docking software to build and evolve a peptide with optimized binding energy to CDCP1. I then synthesized this novel linear peptide in a peptide synthesizer. This research establishes a model for PDC construction to push more accessible and bioavailable drug conjugates.

Source coverage

This record comes from a published award list, not a complete project archive. Its abstract comes from CSEF's public project showcase as archived by the Internet Archive before judging (https://web.archive.org/web/20230401224130/https://ca-csef.zfairs.com/showcase/ShowcaseInfo?f=838e60b7-ea75-46e8-865c-fde4864244b3); the version presented may differ.

Awards (2)

Competition history

  • CSEF 2023 Chemistry · Entry S0618

Resources

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