Azim Abul, Shah Vishal, Doncel Gustavo F, Peterson Nicholas, Gao Wei, Gross Richard
NSF I/UCR Center for Biocatalysis and Bioprocessing of Macromolecules, Polytechnic University, Six Metrotech Center, Brooklyn, New York 11201, USA.
Bioconjug Chem. 2006 Nov-Dec;17(6):1523-9. doi: 10.1021/bc060094n.
Sophorolipids (SLs) are extra cellular glycolipids produced by Candida bombicola ATCC 22214 when grown in the presence of glucose and fatty acids. These compounds have a disaccharide head group connected to a long-chain hydroxyl-fatty acid by a glycosidic bond. To explore structure-activity of modified SLs, a new family of amino acid-SL derivatives was prepared. Synthesized analogs consist of amino acids linked by amide bonds formed between their alpha-amino moiety and the carboxyl group of ring-opened SL fatty acids. Their preparation involved the following: (i) hydrolysis of a natural SL mixture with aqueous alkali to give SL free acids, (ii) coupling of free acids to protected amino acids using dicarbodiimide, and (iii) removing amino acid carboxyl protecting groups. These conjugates were evaluated for their antibacterial, anti-HIV, and spermicidal activity. All tested analogs showed antibacterial activity against both gram +ve and gram -ve organisms. Leucine-conjugated SL was most efficient. For example, the minimum inhibitory concentrations (MIC) for Moraxella sp. and E. coli were 0.83 and 1.67 mg/mL, respectively. Among the alkyl esters of amino acid conjugated SLs, the ethyl ester of leucine-SLs was most active. Against Moraxella sp., S. sanguinis, and M. imperiale, MIC values are 7.62 x 10(-4), 2.28 x 10-(3) and 1.67 mg/mL, respectively. All compounds displayed virus-inactivating activity with 50% effective concentrations (EC50) below 200 microg/mL. The EC50 of leucine-SL ethyl ester was 24.1 microg/mL, showing that it is more potent than commercial spermicide nonoxynol-9 (EC50 approximately 65 microg/mL).
槐糖脂（SLs）是解脂耶氏酵母ATCC 22214在葡萄糖和脂肪酸存在下生长时产生的细胞外糖脂。这些化合物具有通过糖苷键连接到长链羟基脂肪酸的二糖头部基团。为了探索修饰槐糖脂的构效关系，制备了一个新的氨基酸-槐糖脂衍生物家族。合成的类似物由通过其α-氨基部分与开环槐糖脂脂肪酸的羧基之间形成的酰胺键连接的氨基酸组成。它们的制备过程如下：（i）用碱水溶液水解天然槐糖脂混合物以得到槐糖脂游离酸，（ii）使用二碳二亚胺将游离酸与受保护的氨基酸偶联，以及（iii）去除氨基酸羧基保护基团。对这些缀合物的抗菌、抗HIV和杀精活性进行了评估。所有测试的类似物对革兰氏阳性菌和革兰氏阴性菌均显示出抗菌活性。亮氨酸缀合的槐糖脂最有效。例如，对莫拉克斯氏菌属和大肠杆菌的最低抑菌浓度（MIC）分别为0.83和1.67 mg/mL。在氨基酸缀合槐糖脂的烷基酯中，亮氨酸-槐糖脂的乙酯活性最高。对莫拉克斯氏菌属、血链球菌和帝王摩根菌的MIC值分别为7.62×10⁻⁴、2.28×10⁻³和1.67 mg/mL。所有化合物均表现出病毒灭活活性，50%有效浓度（EC50）低于200 μg/mL。亮氨酸-槐糖脂乙酯的EC50为24.1 μg/mL，表明它比市售杀精剂壬苯醇醚-9（EC50约为65 μg/mL）更有效。
