Cyclipostins, novel hormone-sensitive lipase inhibitors from Streptomyces sp DSM 13381 -: II.: Isolation, structure elucidation and biological properties
Cyclipostins, novel hormone-sensitive lipase inhibitors from Streptomyces sp DSM 13381 -: II.: Isolation, structure elucidation and biological properties
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DOI：
10.7164/antibiotics.55.480
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发表时间：
2002-05-01
影响因子：
3.3
通讯作者：
Seibert, G
中科院分区：
文献类型：
--
作者：
Vértesy, L;Beck, B;Seibert, G
激素敏感脂肪酶（HSL）是脂质代谢的关键酶，因此其控制是治疗糖尿病的靶点，链霉菌的培养物DSM 13381已被证明能有效抑制HSL。从这种微生物的菌丝体中分离出10种HSL抑制剂，称为环后蛋白，并检测到另外9种相关化合物。通过二维核磁共振实验和质谱分析表征了它们的结构，发现它们由中性环烯醇磷酸酯和一个额外的γ -内酯环组成。由于其酯结合的脂肪醇侧链，环柱蛋白具有类似于甘油三酯的物理化学性质。环柱蛋白的突出特点是抗hsl活性强，IC50值在纳摩尔范围内。
Hormone-sensitive lipase (HSL) is a key enzyme of lipid metabolism and its control is therefore a target in the treatment of diabetes mellitus, Cultures of the Streptomyces species DSM 13381 have been shown to potently inhibit HSL. Ten inhibitors of HSL, termed cyclipostins, have been isolated from the mycelium of this microorganism and a further nine related compounds detected. Their structures were characterized by 2-D NMR experiments and by mass spectrometry and were found to comprise neutral cyclic enol phosphate esters with an additional gamma-lactone ring. On account of their ester-bound fatty alcohol side chain, the cyclipostins have physicochemical properties similar to those of triglycerides. The outstanding characteristic of the cyclipostins is their strong anti-HSL activity, with IC50 values in the nanomolar range.