Department of Chemistry, New York University, New York, NY 10003-6688, USA.
ChemMedChem. 2012 Jan 2;7(1):114-22. doi: 10.1002/cmdc.201100358. Epub 2011 Sep 23.
We investigated the antimicrobial activities of N-substituted glycine "peptoid" oligomers incorporating cationic and hydrophobic side chains. Head-to-tail macrocyclization was employed to enhance antimicrobial activity. Both linear and cyclic peptoids, ranging from six to ten residues, demonstrate potent antimicrobial activity against Gram-positive and Gram-negative bacteria. These peptoids do not cause significant lysis of human erythrocytes, indicating selective antimicrobial activity. Conformational ordering established upon macrocyclization is generally associated with an enhanced capacity to inhibit bacterial cell growth. Moreover, increased hydrophobic surface area also plays a role in improving antimicrobial activity. We demonstrate the potency of a cyclic peptoid in exerting antimicrobial activity against clinical strains of S. aureus while deterring the emergence of antimicrobial resistance.
我们研究了含有阳离子和疏水性侧链的 N-取代甘氨酸“肽缩醛”低聚物的抗菌活性。采用头到尾的大环化来增强抗菌活性。无论是线性还是环状的肽缩醛，包含六个到十个残基，都表现出对革兰氏阳性和革兰氏阴性细菌的强大抗菌活性。这些肽缩醛不会导致人红细胞显著裂解，表明具有选择性抗菌活性。大环化后建立的构象有序性通常与增强抑制细菌细胞生长的能力相关。此外，增加疏水性表面积也在提高抗菌活性方面发挥作用。我们证明了一种环状肽缩醛在抑制金黄色葡萄球菌临床菌株的抗菌活性方面的效力，同时阻止了抗菌耐药性的出现。
