合成类脂A亚基类似物的酰基取代基对其免疫调节抗病毒活性的影响。

Effect of acyl substituents of synthetic lipid A-subunit analogues on their immunomodulating antiviral activity.

作者信息

Ikeda S, Nishimura C, Matsuura M, Homma J Y, Kiso M, Hasegawa A

机构信息

School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.

出版信息

Antiviral Res. 1990 Jun;13(6):327-33. doi: 10.1016/0166-3542(90)90016-z.

DOI:10.1016/0166-3542(90)90016-z

PMID:1699495

Abstract

A chemically synthesized lipid A-subunit analogue, GLA-60, 2-deoxy-4-O-phosphono-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R)- 3- tetradecanoyloxytetradecanoyl]-D-glucose, has many of the activities of endotoxin but has little toxicity. Then, compounds with various lengths of acyl side chain of the acyloxyacyl group at the 3-O position of GLA-60 were synthesized and evaluated for interferon (IFN)-inducing activity, natural killer (NK) cell activation and antiviral activity. The compounds with acyl side chains between C8 and C15 exhibited significant antiviral activity (inhibition of pox tail lesion formation in vaccinia virus-infected mice), serum IFN-inducing activity and NK cell activation. However, the compound carrying a C2 or a C16 acyl side chain did not exhibit these activities. The compounds with a C13 or C14 acyl side chain showed strong protective against herpes simplex virus type 1 in cyclophosphamide-immunosuppressed mice.

摘要

一种化学合成的脂多糖A亚基类似物GLA - 60，即2 - 脱氧 - 4 - O - 膦酰基 - 2 - [(3R) - 3 - 羟基十四烷酰胺基] - 3 - O - [(3R) - 3 - 十四烷酰氧基十四烷酰基] - D - 葡萄糖，具有许多内毒素的活性，但毒性很小。然后，合成了GLA - 60在3 - O位带有不同长度酰氧基酰基侧链的化合物，并对其诱导干扰素（IFN）活性、自然杀伤（NK）细胞活化和抗病毒活性进行了评估。带有C8至C15之间酰基侧链的化合物表现出显著的抗病毒活性（抑制痘苗病毒感染小鼠的痘苗尾巴损伤形成）、血清IFN诱导活性和NK细胞活化。然而，带有C2或C16酰基侧链的化合物未表现出这些活性。带有C13或C14酰基侧链的化合物在环磷酰胺免疫抑制的小鼠中对1型单纯疱疹病毒显示出强大的保护作用。