CONFORMATION OF HEXADECYLPHOSPHOCHOLINE, AN ANTICANCER DRUG, BY MOLECULAR-DYNAMICS AND NMR METHODS

The conformation of hexadecylphosphocholine (HPC) and its interaction with model membranes prepared from dipalmitoylphosphatidylcholine (DPP C) have been investigated by molecular dynamics (MD) and NMR methods. The results of MD studies indicate that in the global minimum energy s tructure, the phosphocholine head group of the drug is bent at tau(18) and tau(19), while the hexadecyl chain is nearly extended. In the two -dimensional nuclear Overhauser effect (NOE) experiments, intramolecul ar NOEs have been observed between the N-methyl moieties of the head g roup and the methylene protons of the alkyl chain. Such a folding of t he molecule is seen in several of the local minimum energy structures computed by MD simulations, The interaction of HPC with DPPC as studie d by P-31 NMR shows a strong interaction between head groups of the tw o molecules.