Monte Carlo docking simulations of cyclomaltoheptaose and dimethyl cyclomaltoheptaose with paclitaxel

摘要

The molecular basis for the remarkable enhancement of the solubility of paclitaxel by O-dimethylcyclomaltoheptaose (DM-#beta#-CD) over cyclomaltoheptaose (#beta#-cyclodextrin, #beta#-CD) was investigated with Monte Carlo docking-minimization simulation. As possible guests of inclusion complexation for the host cyclic oligosaccharides, two functional moieties of the suggested solution structure of paclitaxel were used one is the C-3'N benzoyl moiety (B-ring) and the other is a hydrophobic (HP) cluster site among the C-3'- phenyl (C-ring), C-2 benzoate (A-ring), and C-4 acetoxy moieties. The energetic preference of inclusion complexation of DM-#beta#-CD over #beta#-CD was analyzed on the basis of more efficient partitioning process of DM-#beta#-CD into the hydrophobic cluster site of the paclitaxel.