Department of Chemistry, State University of New York-ESF, Syracuse, NY 13210, United States.
Bioorg Med Chem Lett. 2012 Jan 15;22(2):811-3. doi: 10.1016/j.bmcl.2011.12.055. Epub 2011 Dec 17.
HMBPP ((E)-4-hydroxy-3-methyl-2-butenyl pyrophosphate) is a highly potent innate immunogen that stimulates human γδ T cells expressing the Vγ2Vδ2 T cell antigen receptor. To determine if glycoside conjugates of HMBPP retain activity, the 4-β-glucoside and its acetylated homolog were synthesized and tested for their ability to stimulate γδ T cells. The glycoside HMBPP conjugate stimulated human γδ T cells with an EC(50) of 78nM. The tetraacetyl glycoside HMBPP conjugate was also active (EC(50)=360nM). The two isomeric mono-β-glucosides of the parent (E)-2-methylbut-2-ene-1,4-diol, however, were not active. Thus, HMBPP glycosylated at the 4-OH position stimulates γδ T cells as long as the pyrophosphate moiety is present.
HMBPP((E)-4-羟基-3-甲基-2-丁烯基焦磷酸酯)是一种强效的天然免疫原，可刺激表达 Vγ2Vδ2 T 细胞抗原受体的人类 γδ T 细胞。为了确定 HMBPP 的糖苷缀合物是否保留活性，合成了 4-β-葡萄糖苷及其乙酰化类似物，并测试了它们刺激 γδ T 细胞的能力。糖苷 HMBPP 缀合物以 78nM 的 EC(50)刺激人类 γδ T 细胞。四乙酰基糖苷 HMBPP 缀合物也具有活性(EC(50)=360nM)。然而，母体 (E)-2-甲基-2-丁烯-1,4-二醇的两种非对映异构体单-β-葡萄糖苷没有活性。因此，只要焦磷酸部分存在，4-OH 位糖基化的 HMBPP 就可以刺激 γδ T 细胞。
