A switch in N-terminal capping of β-peptides creates novel self-assembled nanoparticles

Yi-Kai Chen; Isabella A Simon; Ivan Maslov; Ivan E Oyarce-Pino; Ketav Kulkarni; Denham Hopper; Marie-Isabel Aguilar; Naveen Vankadari; Brad Rs Broughton; Mark P Del Borgo

doi:10.1039/d3ra04514e

A switch in N-terminal capping of β-peptides creates novel self-assembled nanoparticles

RSC Adv. 2023 Oct 9;13(42):29401-29407. doi: 10.1039/d3ra04514e. eCollection 2023 Oct 4.

Authors

Yi-Kai Chen^{1

2}, Isabella A Simon^{1

2}, Ivan Maslov^{1

2}, Ivan E Oyarce-Pino^{1

2}, Ketav Kulkarni^{3

2}, Denham Hopper^{1

2}, Marie-Isabel Aguilar^{3

2}, Naveen Vankadari⁴, Brad Rs Broughton^{1

2}, Mark P Del Borgo^{1

2}

Affiliations

¹ Department of Pharmacology, Monash University Clayton VIC 3800 Australia mark.delborgo@monash.edu.
² Biomedicine Discovery Institute, Monash University Clayton VIC 3800 Australia.
³ Department of Biochemistry & Molecular Biology, Monash University Clayton VIC 3800 Australia.
⁴ Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne Melbourne VIC 3000 Australia.

Abstract

Small tripeptides composed entirely of β³-amino acids have been shown to self-assemble into fibres following acylation of the N-terminus. Given the use of Fmoc as a strategy to initiate self-assembly in α-peptides, we hypothesized that the acyl cap can be replaced by an Fmoc without perturbation to the self-assembly and enable simpler synthetic protocols. We therefore replaced the N-acyl cap for an Fmoc group and herein we show that these Fmoc-protected β³-peptides produce regular spherical particles, rather than fibrous structures, that are stable and capable of encapsulating cargo. We then demonstrated that these particles were able to deliver cargo to cells without any obvious signs of cytotoxicity. This is the first description of such regular nanoparticles derived from Fmoc-protected β³-peptides.