Institute of Functional Interfaces, Karlsruhe Institute of Technology (KIT), 76344 Eggenstein Leopoldshafen, Germany.
Department of Pharmacy, National University of Singapore, 117544 Singapore, Singapore.
Front Biosci (Landmark Ed). 2022 Feb 14;27(2):64. doi: 10.31083/j.fbl2702064.
Antimicrobial peptides (AMPs) are short, cationic, amphipathic molecules that have gained tremendous popularity as alternatives to traditional antibiotics due to their lower propensity to develop bacterial resistance. However, the clinical developability of AMPs remains impeded due to shortcomings such as proteolytic instability and poor penetration leading to low bioavailability.
To improve the access of AMPs to cells and subsequent bacteria killing, we evaluated the cell-penetrating and antimicrobial properties of three novel libraries of synthetic peptoids using Minimum Inhibitory Concentration, killing efficacy and membrane permeabilization assays against mycobacteria and . In addition, we investigated cell selectivity using mammalian cells to assess peptoid toxicity.
We showed that short tetrameric Rhodamine B-labeled peptoids composed of a balance of aromatic and lipophilic residues have potent selective antimicrobial activity against a range of microorganisms. The most potent candidates were active against drug-resistant isolates as well as mycobacterial strains, with cell penetrating capabilities reported in HeLa and RAW 264.7 macrophage cells.
These data suggest that peptoids with novel dual functionalities may potentially be an interesting class of therapeutics and/or molecular delivery agents for anti-infective purposes.
抗菌肽 (AMPs) 是短链、阳离子、两亲性分子，由于其不易产生细菌耐药性，因此作为传统抗生素的替代品而备受关注。然而，由于酶解稳定性差和穿透性差导致生物利用度低等缺点，抗菌肽的临床开发仍然受到阻碍。
为了提高抗菌肽进入细胞和随后杀死细菌的能力，我们使用最小抑菌浓度 (MIC)、杀菌效果和膜通透性测定法，评估了三种新型合成肽的细胞穿透性和抗菌特性。此外，我们使用哺乳动物细胞评估了肽的细胞选择性，以评估其毒性。
我们表明，由芳香族和疏水性残基平衡组成的短四聚体 Rhodamine B 标记肽具有针对多种微生物的强大选择性抗菌活性。最有效的候选物对耐药 分离株以及分枝杆菌菌株具有活性，并且在 HeLa 和 RAW 264.7 巨噬细胞中报告了细胞穿透能力。
这些数据表明，具有新型双重功能的肽可能是一种有前途的治疗剂和/或用于抗感染目的的分子传递剂。
