Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

“DROGOES” - Beyond Conventional: Exploring the Potential of Cell-Penetrating Peptides for Target-Based Drug Delivery

Version 1 : Received: 18 October 2024 / Approved: 21 October 2024 / Online: 21 October 2024 (08:07:48 CEST)

How to cite: S S, G.; Mohan, A.; Naisam, S.; Selvin, S.; Sreekumar, N. “DROGOES” - Beyond Conventional: Exploring the Potential of Cell-Penetrating Peptides for Target-Based Drug Delivery . Preprints 2024, 2024101571. https://doi.org/10.20944/preprints202410.1571.v1 S S, G.; Mohan, A.; Naisam, S.; Selvin, S.; Sreekumar, N. “DROGOES” - Beyond Conventional: Exploring the Potential of Cell-Penetrating Peptides for Target-Based Drug Delivery . Preprints 2024, 2024101571. https://doi.org/10.20944/preprints202410.1571.v1

Abstract

The study explores the potential of Cell-Penetrating Peptides (CPPs) for targeted drug delivery, particularly in anticancer applications. Despite certain drawbacks, such as short duration of action and poor stability in vivo, CPPs show promise when optimized through chemical modification or clever design. Advancements in targeted drug delivery using CPPs, especially for transporting anticancer drugs and imaging reagents, highlight their evolving efficacy. Four different CPP chains (7 alpha, 7 beta, 12 alpha, and 12 beta) and four in-house anticancer lead molecules were considered for the study. The CPPs were modeled and validated for in silico interaction analysis. Targeting proteins crucial in cell growth and signaling pathways, such as ADRM1, PSMD4, CDK1, CDK2, CDK4, CDK6, P53, and EGFR, presents a significant therapeutic opportunity. The in silico molecular interaction analysis involving CPP-conjugated lead molecules and these targets indicates favorable binding affinities, particularly with beta-confirmation 12 and 7 peptide chains. Notably, CPP conjugation enhances interactions without compromising ligand potentiality. This delicate balance emphasizes the role of CPPs in augmenting protein-ligand interactions, suggesting their potential benefits in targeted drug delivery, pending further optimization and experimental validation.

Keywords

cell penetrating peptides; phytocompounds; targeted drug delivery; anticancer

Subject

Biology and Life Sciences, Life Sciences

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