Partition of amphiphilic molecules to lipid bilayers by ITC: Low-affinity solutes

MORA, MARIA JULIA; GRANERO, GLADYS ESTER; MORENO, MARIA JOÃO; SAMELO, JAIME; MORA, MARIA JULIA; GRANERO, GLADYS ESTER; MORENO, MARIA JOÃO; SAMELO, JAIME

ACS Omega

American Chemical Society

Año: 2017 vol. 2 p. 6863 - 6869

2470-1343

A protocol is developed to allow the accurate characterization of partition to lipid bilayers for solutes with low affinity, using isothermal titration calorimetry. The methodology proposed is suitable for studies using complex membranes, such as intact biomembranes or whole cells. In the method developed, the association is characterized at increasing solute concentrations. This allows the characterization of solute partition into unperturbed membranes, as well as effects induced by high solute concentrations. Most druglike molecules are expected to interact with lowto-moderate affinity with relevant cell membranes. This is due to both the need for a relatively high aqueous solubility of the drug and the poor binding properties of the cell membranes. The methodology is applied to characterize the interaction of antibiotic Rifampicin with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and with lipid bilayers representative of bacterial membranes.