Violette Aude, Fournel Sylvie, Lamour Karen, Chaloin Olivier, Frisch Benoit, Briand Jean-Paul, Monteil Henri, Guichard Gilles
Immunologie et Chimie Thérapeutiques, UPR 9021 CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, F-67084 Strasbourg Cedex, France.
Chem Biol. 2006 May;13(5):531-8. doi: 10.1016/j.chembiol.2006.03.009.
Unnatural oligomeric scaffolds designed to adopt defined secondary structures (e.g., helices), while retaining the chemical diversity of amino acid side chains, are of practical value to elaborate functional mimetics of bioactive alpha-polypeptides. Enantiopure N,N'-linked oligoureas as short as seven residues long have been previously shown to fold into a stable helical structure, stabilized by 12- and 14-membered H-bonded rings. We now report that eight-residue oligoureas designed to mimic globally amphiphilic alpha-helical host-defense peptides are effective against both gram-negative and gram-positive bacteria (including methicillin-resistant Staphylococcus aureus [MRSA]) and exhibit selectivity for bacterial versus mammalian cells. Circular dichroism (CD) spectroscopy studies suggest enhanced helical propensity of oligoureas in the presence of phospholipid vesicles. The utility of this new class of nonpeptidic foldamers for biological applications is highlighted by high resistance to proteolytic degradation.
设计为具有特定二级结构（如螺旋）的非天然低聚支架，同时保留氨基酸侧链的化学多样性，对于精心构建生物活性α-多肽的功能模拟物具有实际价值。先前已表明，短至七个残基的对映体纯N，N'-连接的低聚脲可折叠成稳定的螺旋结构，并由12元和14元氢键环稳定。我们现在报告，设计用于模拟全局两亲性α-螺旋宿主防御肽的八残基低聚脲对革兰氏阴性菌和革兰氏阳性菌（包括耐甲氧西林金黄色葡萄球菌[MRSA]）均有效，并且对细菌与哺乳动物细胞具有选择性。圆二色性（CD）光谱研究表明，在磷脂囊泡存在下，低聚脲的螺旋倾向增强。对蛋白水解降解的高抗性突出了这类新型非肽折叠体在生物学应用中的实用性。
