Investigating Penetration and Antimicrobial Activity of Vector-Bicycle Conjugates

New publication in Infectious Diseases:

SB-PEPTIDE, a division of Smartox Biotechnology dedicated to custom peptide synthesis services, has been cited once again as a key peptide supplier in an innovative new scientific publication. This publication addresses the urgent issue of growing antibiotic resistance, particularly for Gram-negative infections. They investigate how conjugating membrane-active peptides (MAPs) derived from ixosin-B can enhance the penetration and antiviral activity of Bicycle molecules — a potential new class of antibiotics. The study highlights the importance of peptides as vectors for delivering Bicycle molecules and underscores Smartox‘s commitment to advancing scientific research through their custom peptide synthesis services.

Abstract:
Growing antibiotic resistance is rapidly threatening the efficacy of treatments for Gram-negative infections. Bicycle molecules, constrained bicyclic peptides from diverse libraries generated by bacteriophage display that bind with high affinity to a chosen target are a potential new class of antibiotics. The generally impermeable bacterial outer membrane currently limits the access of peptides to bacteria. The conjugation of membrane active peptides offers an avenue for outer membrane penetration. Here, we investigate which physicochemical properties of a specific membrane active peptide (MAP), derived from ixosin-B, could be tweaked to enhance the penetration of conjugates by generating multiple MAP-Bicycle conjugate variants. We demonstrate that charge and hydrophobicity are important factors, which enhance penetration and, therefore, antimicrobial potency. Interestingly, we show that induction of secondary structure, but not a change in amphipathicity, is vital for effective penetration of the Gram-negative outer membrane. These results offer insights into the ways vectors could be designed to deliver Bicycle molecules (and other cargos) through biological membranes.

https://pubs.acs.org/doi/10.1021/acsinfecdis.3c00427

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