How hydrogen bonds impact P-glycoprotein transport and permeability

作者：Prashant Desai, Thomas J. Raub, Marı́a-Jesús Blanco · 发表于：Bioorganic & Medicinal Chemistry Letters · 年份：2012 · DOI：10.1016/j.bmcl.2012.08.059 · 被引用次数：141 · 研究领域：Drug Transport and Resistance Mechanisms、DNA and Nucleic Acid Chemistry、Carbohydrate Chemistry and Synthesis

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.