Solubilization of Paclitaxel (taxol) by peptoad self-assemblies

A molecular dynamics simulation was carried out involving a paclitaxel molecule, 987 peptoad molecules, and 35 938 water molecules (conditions shown experimentally to effect paclitaxel solubilization in water). The peptoads are shown to form large clumps, the centers of which are dry and thus favorable to hydrogen bonding between paclitaxel and peptoads. Hydrogen-bonding equilibrium among the peptoads themselves in the developing clumps is achieved in 2 ns. The number and position of hydrogen bonds between the paclitaxel and peptoads fluctuate randomly from two to six within a 2-5 ns time frame. Hydrophobic association between the peptoad chains and the apolar paclitaxel groups does not seem to be an important element of the solubilization. Instead, the hydrophobic chains of the peptoads encasing the paclitaxel extend outward into the dry interior of the peptoad clump where other chains in the clump are located. One hopes that studies such as this will ultimately allow rational predictions when designing new and specific drug solubilizers.