title: How hydrogen bonds impact P-glycoprotein transport and permeability.
abstract: The requirement to cross a biological membrane can be a complex process especially if multidrug transporters such as P-gp must be considered. Drug partitioning into the lipid membrane and efflux by P-gp are tightly coupled processes wherein H-bonding interactions play a key role. All H-bond donors and acceptors are not equal in terms of the strength of the H-bonds that they form, hence it is important to consider their relative strength. Using various examples from literature, we illustrate the benefits of considering the relative strengths of individual H-bonds and introducing intramolecular H-bonds to increase membrane permeability and/or decrease P-gp efflux.
authors.affiliation: Computational ADME, Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Prashant V
authors.initials: PV
authors.lastname: Desai
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Raub
authors.forename: Maria-Jesus
authors.initials: MJ
authors.lastname: Blanco
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001692:Biological Transport; D006860:Hydrogen Bonding; D015394:Molecular Structure; D010539:Permeability
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1