Structural Element of Vitamin U‐Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections

Abstract

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving a much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium‐based polypeptides with different arms and degrees of polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2‐PM‐1H+, shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in “Angew. Chem. Int. Ed., 2020, 59, 6412.”), which can be attributed to the high positive density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2‐PM‐1H+ is primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram‐positive or gram‐negative bacteria in a mixed‐bacteria model. Additionally, both in vitro and in vivo experiments demonstrate that G2‐PM‐1H+ exhibits superior efficacy against methicillin‐resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2‐PM‐1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.

Organic–Inorganic Heterointerface-Expediting Electron Transfer Realizes Efficient Plasmonic Catalytic Sterilization via a Carbon-Dot Nanozyme

“…coli and Gram-positive S. aureus, place an enormous burden on public health and the social economy owing to their high invasiveness and ubiquity in daily life. , In view of the excellent plasmonic catalysis and localized heating of the FeCG nanozyme, we first investigated the antibacterial activity of plasmonic FeCG against E. coli and S.…”

A universal strategy to enhance photothermal conversion efficiency by regulating the molecular aggregation states for safe photothermal therapy of bacterial infections

“…4–7 As a result, there is an urgent need for the development of antibiotic-independent treatments for bacterial infections. 8–11 In view of the non-invasive attribute, high selectivity, deep tissue penetration, less drug resistance, and broad-spectrum antibacterial properties, near-infrared (NIR)-based photothermal therapy (PTT) has emerged as a pivotal approach for effectively combating drug-resistant bacterial infections. 12–15 Nevertheless, conventional organic photothermal agents (PTAs) often exhibit low photothermal conversion efficiencies (PCEs), necessitating an increase in either PTA concentrations or laser power densities to achieve ideal therapeutic outcomes.…”

Conformation-Switchable Polypeptides as Molecular Gates for Controllable Drug Release

“…Synthetic polypeptides have displayed great potentials in the biomedical field and are regarded as promising candidates for the design of drug carriers due to their desired biocompatibility and biodegradability. − As protein mimics, polypeptides can adopt ordered secondary structures (e.g., α-helix and β-sheet) through hydrogen bonding interactions between backbone peptide bonds, − which endow them with conformation-specific assembly behaviors and biomedical functions. − For instance, cationic polypeptides with α-helical structures exhibit much higher membrane-penetrating activity than their random-coiled analogues, which are internalized through the “pore-formation” mechanism. − Through proper side-chain design, α-helical, cationic polypeptides have been widely studied to promote the intracellular delivery of molecular cargos or to facilitate the design of antimicrobial or antitumor polymers. − Additionally, amphiphilic polypeptides with α-helical hydrophobic segments tend to self-assemble into vesicles due to the parallel arrangement of rigid helices, while their β-sheet and random-coiled analogues are more likely to form micelles. ,, Due to the distinct differences of materials properties between helical and random-coiled conformation, conformation-switchable polypeptides are designed and synthesized to manipulate their biomedical functions in situ . The transition of secondary structures is achieved through the fine-tuning of side-chain interactions including electrostatic interactions, − polarity, − hydrogen bonds, coordination interaction, and base-pairing interactions, which activates or deactivates the helix-associated functions under desired conditions.…”