Silva Nigenda Ezequiel, Postma Tobias M, Hezwani Mohammed, Pirvan Alin, Gannon Susan, Smith Carol-Anne, Riehle Mathis, Liskamp Rob M J
School of Chemistry , University of Glasgow , Joseph Black Building, University Avenue , Glasgow G12 8QQ , UK . Email:
Centre for Cell Engineering , Institute of Molecular, Cell and Systems Biology , Joseph Black Building, University Avenue , Glasgow G12 8QQ , UK.
Medchemcomm. 2018 May 9;9(6):982-987. doi: 10.1039/c8md00113h. eCollection 2018 Jun 1.
A new category of phosphonium based cationic amphiphilic peptides has been developed and evaluated as potential antimicrobial peptides and cell penetrating peptides. The required building blocks were conveniently accessible from cysteine and could be applied in a solid phase peptide synthesis protocol for incorporation into peptide sequences. Evaluation of the antimicrobial properties and cellular toxicity of these phosphonium based peptides showed that these "soft" cationic side-chain containing peptides have poor antimicrobial properties and most of them were virtually non toxic (on HEK cells tested at 256 and 512 μM) and non-haemolytic (on horse erythrocytes tested at 512 μM), hinting at an interesting potential application as cell penetrating peptides. This possibility was evaluated using fluorescent peptide derivatives and showed that these phosphonium based peptide derivatives were capable of entering HEK cells and depending on the sequence confined to specific cellular areas.
已开发出一类新型的基于鏻的阳离子两亲性肽，并将其作为潜在的抗菌肽和细胞穿透肽进行了评估。所需的构建模块可方便地从半胱氨酸获得，并可应用于固相肽合成方案中，以掺入肽序列。对这些基于鏻的肽的抗菌性能和细胞毒性的评估表明，这些含有“软”阳离子侧链的肽抗菌性能较差，其中大多数实际上无毒（在256和512μM下对HEK细胞进行测试）且无溶血作用（在512μM下对马红细胞进行测试），这暗示了其作为细胞穿透肽的有趣潜在应用。使用荧光肽衍生物对这种可能性进行了评估，结果表明这些基于鏻的肽衍生物能够进入HEK细胞，并根据序列局限于特定的细胞区域。
