Lee J, Lewin N E, Blumberg P M, Marquez V E
College of Pharmacy, Seoul National University, Korea.
Arch Pharm Res. 1998 Apr;21(2):164-7. doi: 10.1007/BF02974022.
Bis-gamma-lactones (1, 2) having a perhydrofuro[3,4-c]furan-1,4-dione skeleton were designed as conformationally constrained diacylglycerol analogues. They were synthesized from D-apiose in 11 steps, and evaluated as PKC-alpha ligands by measuring their ability to displace bound [3H]-PDBU from the enzyme. The compounds showed moderate binding affinities with Ki values of 13.89 (+/- 5.67) microM and 11.47 (+/- 0.89) microM, respectively. Their similar binding affinities indicate that these two bicyclic compounds were not effectively discriminated by PKC-alpha in terms of the direction of the side chain as other ligands built on similar bis-gamma-lactones.
具有全氢呋喃并[3,4-c]呋喃-1,4-二酮骨架的双γ-内酯（1,2）被设计为构象受限的二酰基甘油类似物。它们由D-阿糖合成，共11步，并通过测量其从酶中置换结合的[3H]-PDBU的能力来评估其作为蛋白激酶C-α（PKC-α）配体的活性。这些化合物表现出中等的结合亲和力，Ki值分别为13.89（±5.67）μM和11.47（±0.89）μM。它们相似的结合亲和力表明，与基于类似双γ-内酯构建的其他配体相比，这两种双环化合物在侧链方向上未被PKC-α有效区分。
