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Discovery and Characterization of Anti-cancer Peptides from a Random Peptide Library

Pavan Kumar Puvvula, Anne M. Moon.

Abstract

We performed a forward genetic screen to discover peptides that specifically target breast cancer cells using a Penetratin tagged, random 15mer peptide library. We identified a group of novel peptides that specifically inhibited the proliferation and survival of breast cancer cells without affecting normal primary mammary epithelial cells or fibroblasts. The intrinsic apoptotic pathway is activated by these peptides in the face of abnormal expression of numerous cell cycle regulatory genes.

Introduction:

Cell-penetrating peptides (CPPs) are comprised of amino acids that function as carrier molecules to transduce various cargo molecules across cell membranes. In the recent past, several potential anti-cancer therapeutic peptides have come to light utilizing the advantages of CPPs. The main principle underlying these discoveries is the identification of dominant-negative domains of proteins with anti-cancer properties.

Discussion:

We recently demonstrated that RNA-binding domains of hnRNPU, RBM39 and hnRNPK inhibit the survival of a range of cancer cells. Here we established an unbiased method to discover peptides with anti-cancer properties. Previously, several studies have explored the benefits of random peptide libraries with the phage display technique to identify cancer cell-specific ligands.

The main drawback in these studies was the lack of a tag or peptide to facilitate cargo penetration and intracellular distribution; here we employed the Penetratin tag to overcome this issue. Our results show that a subset of the random peptides we generated disrupt breast cancer cell proliferation and survival without affecting normal cells.

Acknowledgments:

We thank the Weis Center for Research at Geisinger Clinic for supporting this project.

Citation: Puvvula PK, Moon AM (2024) Discovery and characterization of anti-cancer peptides from a random peptide library. PLoS ONE 19(2): e0293072. https://doi.org/10.1371/journal.pone.0293072

Editor: Arunava Roy, University of South Florida, UNITED STATES

Received: July 20, 2023; Accepted: October 3, 2023; Published: February 13, 2024.

Copyright: © 2024 Puvvula, Moon. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

 

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