tripeptide arginyl-glycyl-aspartic acid (rgd) for delivery ofcyclophosphamide anticancer drug: a computational approach

Density functional theory (dft) calculations were performed on tripeptide arginyl-glycyl-aspartic acid(rgd) as an efficient drug carrier to deliver the commercially famous cyclophosphamide (cp) anticancerdrug within ethanol solution. the most negative binding energy (-5.22 kcal/mol) was measured for thecp-rgd-7 created through the h-bond interaction between the p=o (phosphoryl) oxygen atom of thecp and hydrogen atom of o-h group in the rgd. the quantum theory of atoms in molecules (qtaim)proved that the cp-rgd-6 was composed of five intra-molecular ch…hc, n…hc and nh…oc plusone inter-molecular nh…n interactions. among cp-rgd-6, cp-rgd-7 and cp-rgd-8 with the smallestbinding energies (highest structural stabilities), the cp-rgd-6 showed the minimum hardness, energy gapand chemical potential whereas the utmost electrophilicity index and electronegativity which confirmed itcould the most effectively be bound onto the cancer cells. consequently, among twenty designed carriers, thecp-rgd-6 was recognized as the most promising drug delivery system. according to the results achievedfrom the molecular dynamics (md) simulations performed in ethanol solvent on the cp-rgd-peg systemscontaining different number of peg chains, it was established that the cp-rgd-6peg cell was the mostsuitable vehicle with desirable fv (4988.89 å3) and ffv (22.66%) values as well as small drug diffusioncoefficient (0.0114×10^–5 cm^2/s) indicating low drug release rate.