SialoPen peptides are new cationic foldamers with remarkable cell permeability

I Abrrey Monreal; Erik M Contreras; Gary A Wayman; Hector C Aguilar; Jonel P Saludes

doi:10.1016/j.heliyon.2020.e05780

SialoPen peptides are new cationic foldamers with remarkable cell permeability

Heliyon. 2020 Dec 24;6(12):e05780. doi: 10.1016/j.heliyon.2020.e05780. eCollection 2020 Dec.

Authors

I Abrrey Monreal^{1

2}, Erik M Contreras^{1

2}, Gary A Wayman³, Hector C Aguilar¹, Jonel P Saludes^{2

4

5}

Affiliations

¹ Immunology and Microbiology Department, Cornell University, Ithaca, NY 14850, USA.
² Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
³ Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164, USA.
⁴ Center for Natural Drug Discovery & Development (CND3) and Department of Chemistry, University of San Agustin, Iloilo City, 5000, Philippines.
⁵ Balik Scientist Program, Philippine Council for Health Research & Development (PCHRD), Department of Science and Technology, Bicutan, Taguig, 1631, Philippines.

Abstract

The ability to access intracellular targets is of vital importance as the number of identified druggable intracellular targets increases every year. However, intracellular delivery poses a formidable barrier, as many potential therapeutics are impermeable to cell membranes, which hinders their practical application in drug development. Herein we present de novo-designed unnatural cell penetrating peptide foldamers utilizing a 2,3-Didehydro-2-deoxyneuraminic acid (Neu2en) scaffold. Conveniently, this scaffold is amenable to standard Fmoc-based solid-phase peptide synthesis, with the advantages of tunable secondary structures and enhanced biostability. Flow cytometry and live-cell confocal microscopy studies showed that these Neu2en-based peptides, hereinafter termed SialoPen peptides, have significantly superior uptake in HeLa and primary neuronal hippocampal cells, outperforming the classical cell permeable peptides penetratin and HIV-TAT.

Keywords: Biological sciences; Cargo transport; Cell penetrating peptides; Drug delivery; Foldamer; Health sciences; Helical; Infectious disease; Neuron translocation; Polymer; Public health; SPPS; Sialic acid; Unnatural amino acid; Virology.

Abstract

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