Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Chemistry. 2010 Apr 12;16(14):4259-65. doi: 10.1002/chem.200902984.
The cyclic decapeptide gramicidin S (GS) was used as a model for the evaluation of four turn mimetics. For this purpose, one of the D-Phe-Pro two-residue turn motifs in the rigid cyclic beta-hairpin structure of GS was replaced with morpholine amino acids (MAA 2-5), differing in stereochemistry and length of the side-chain. The conformational properties of the thus obtained GS analogues (6-9) was assessed by using NMR spectroscopy and X-ray crystallography, and correlated with their biological properties (antimicrobial and hemolytic activity). We show that compound 8, containing the dipeptide isostere trans-MAA 4, has an apparent high structural resemblance with GS and that its antibacterial activity against a panel of Gram positive and -negative bacterial strains is better than the derivatives 6, 7 and 9.
环状十肽短杆菌素 S（GS）被用作评估四个转角类似物的模型。为此，在 GS 的刚性环 β-发夹结构中，用具有不同立体化学和侧链长度的吗啉氨基酸（MAA2-5）取代了 D-Phe-Pro 二肽转角模体。通过使用 NMR 光谱和 X 射线晶体学评估了所得 GS 类似物（6-9）的构象性质，并将其与生物性质（抗菌和溶血活性）相关联。我们表明，含有二肽等排体反式-MAA4 的化合物 8 与 GS 具有明显的高结构相似性，并且其对一系列革兰氏阳性和阴性细菌菌株的抗菌活性优于衍生物 6、7 和 9。
