Journal
ACS OMEGA
Volume 2, Issue 10, Pages 6863-6869Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsomega.7b01145
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Funding
- Portuguese Fundacao para a Ciencia e a Tecnologia (FCT) [007630 UID/QUI/00313/2013, PT2020_PTDC_DTP-FTO_2784_2014]
- ERASMUS MUNDUS Action 2. PRECIoSA: Programe of Exchange & Cooperation for International Studies [2012-246/001-001-EMA2]
- [COM-PETE2020-UE]
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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 low-to-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.
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