Joint experimental and theoretical investigation of the propensity of peptoids as drug carriers

Transport across the membrane is one of the key obstacles drug molecules must overcome to effectively function in the cell. Potential drugs should therefore be designed taking into account these specific membrane-transport properties. Here we investigate, both experimentally and by simulation, one promising class of molecules. Peptoids are structural analogs of the amino acids that make up the proteins of the cell. They constitute a very promising class of drug carriers because they are known to cross several biological barriers and, unlike proteins, they are unaffected by proteases. All-atom molecular dynamics simulations demonstrate that even short peptoid molecules exist in a rapidly fluctuating conformational ensemble, which differentially presents hydrophobic and hydrophilic molecular surface area to its environment, making these molecules well suited candidates for tunable membrane transport. In vivo studies showed that the synthesized peptoid Fluo-{6,6,6,6,6,6}-NH2 efficiently translocates into the cells and accumulates preferably in the cytosol.