Researchers have used nuclear Magnetic Resonance (NMR) to study shape-shifting movement of molecules, a feature that potentially could help drug designers overcome issues of resistance, transportation of drugs to targets and oral bioavailability, according to research published in the April issue of the Journal of the American Chemical Society.
In the study, Jeffrey Peng, PhD, associate professor of chemistry and biochemistry at University of Notre Dame in South Bend, Ind., and colleagues described an approach for ligand flexibility activity studies using nuclear MR spin relaxation.
Peng and colleagues demonstrated that the flexibility changes reflect conformational reorganization by studying three structurally similar but flexibly differentiated ligands of human Pin1, a peptidyl-prolyl isomerase.
The study of flexibility-activity relationships adds another dimension to the longstanding structure-activity relationships that scientists have studied, according to Peng.
"We need experimental methods that can tell us, systematically, how architectural changes in the candidate drug molecule can change its flexibility relevant for drug-like properties. These methods would benefit not just one particular kind of disease but basically drug design in general," including therapies for cancer, AIDS and MRSA, noted Peng.