标题：A novel soluble analog of the HIV-1 fusion cofactor, globotriaosylceramide (Gb3), eliminates the cholesterol requirement for high affinity gp120/Gb3 interaction
出版社：American Society for Biochemistry and Molecular Biology
摘要：We have analyzed the interaction of adamantyl Gb3 (adaGb3), a semi-synthetic soluble analog of Gb3, with HIV-1 surface envelope glycoprotein gp120. In this analog, which was orginally designed to inhibit verotoxin binding to its glycolipid receptor, Gb3, the fatty acid chain is replaced with a rigid globular hydrocarbon frame (adamantane). Despite its solubility, adaGb3 forms monolayers at an air-water interface. Compression isotherms of such monolayers demonstrated that the adamantane substitution resulted in a larger minimum molecular area and a more rigid, less compressible film than Gb3. Insertion of gp120 into adaGb3 monolayers was exponential whereas the gp120/Gb3 interaction curve was sigmoidal with a lag phase of 40 min. Adding cholesterol into authentic Gb3 monolayers abrogated the lag phase and increased the initial rate of interaction with gp120. This effect of cholesterol was not observed with phosphatidylcholine or sphingomyelin. In addition, verotoxin-bound adaGb3 or Gb3 plus cholesterol was recovered in fractions of comparable low density after ultracentrifugation through sucrose-density gradients in the presence of Triton X-100. The unique biological and physico-chemical properties of adaGb3 suggest that this analog may be a potent soluble mimic of Gb3, providing a novel concept for developing GSL-derived viral fusion inhibitors.
