Membrane‐acting biomimetic peptoids against visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) is among the most neglected tropical diseases in the world. Drug cell permeability is essential for killing the intracellular residing parasites responsible for VL, making cell‐permeating peptides a logical choice to address VL. Unfortunately, the limited biological stability of peptides restricts their usage. Sequence‐specific oligo‐N‐substituted glycines (‘peptoids’) are a class of peptide mimics that offers an excellent alternative to peptides in terms of ease of synthesis and good biostability. We tested peptoids against the parasite Leishmania donovani in both forms, that is, intracellular amastigotes and promastigotes. N‐alkyl hydrophobic chain addition (lipidation) and bromination of oligopeptoids yielded compounds with good antileishmanial activity against both forms, showing the promise of these antiparasitic peptoids as potential drug candidates to treat VL.

Interdisciplinary‐Inspired Smart Antibacterial Materials and Their Biomedical Applications

“…Therefore, AMPs with new actions such as penetration instead of disruption or lysis, have been developed. [ 57,191 ] Zhang et al. have modified the structure of poly‐β‐L‐lysine to penetrate the bacterial cell membrane instead of disrupting it.…”

“…Therefore, AMPs with new actions such as penetration instead of disruption or lysis, have been developed. [57,191] Zhang et al have modified the structure of poly-𝛽-L-lysine to penetrate the bacterial cell membrane instead of disrupting it. [192] The modified AMP shows lower toxicity toward host cells and avoids the development of resistance against S. aureus even after more than 480 generations.…”

The activity of antimicrobial peptoids against multidrug-resistant ocular pathogens

“…For example, peptoids can have minimum inhibitory concentrations as low as 1.8 μg mL −1 against Bacillus subtilis and 12.4 μg mL −1 against Escherichia coli , whereas these bacteria had MICs of 4.5 μg mL −1 and 35.6 μg mL −1 , respectively, with the AMP melittin [ 31 ] Di-guanidine peptoids, produced via acid amine-coupling between naphthyl-indole amine and with different amino acids were more potent against S. aureus , giving MICs of 2.1–6.4 μg mL −1 compared to the MIC of ciprofloxacin which ranged from 8 to 256 μg mL −1 [ 38 ]. Furthermore, peptoids can be active against all the ESKAPE pathogens [ 39 ], which are the primary cause of nosocomial (hospital-acquired) infections, as well as bacterial persister cells [ 40 ], viruses [ 41 ], fungi [ 40 ], and parasites [ 42 ]. Peptoids also exhibit low immunogenicity akin to AMPs [ 43 , 44 ].…”

Peptide-mimetic treatment ofPseudomonas aeruginosain a mouse model of respiratory infection

“…Since AMPs are easily manipulated and their structures are so tightly connected to their efficacy, creating peptidomimetics provides an untapped reservoir of antimicrobial therapeutic solutions. We have previously developed a class of AMP derivates known as peptoids, or N -substituted glycine oligomer peptidomimetics, based off LL-37 36–39 . Peptoids differ from peptides in that the side chains are linked to the amide in the backbone instead of the α-carbon.…”