Structural biology and function of solute transporters: implications for identifying and designing substrates |
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Authors: | Zhang Eric Y Knipp Gregory T Ekins Sean Swaan Peter W |
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Institution: | Division of Pharmaceutics, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210-1291, USA. |
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Abstract: | Solute carrier (SLC) proteins have critical physiological roles in nutrient transport and may be utilized as a mechanism to increase drug absorption. However, we have little understanding of these proteins at the molecular level due to the absence of high-resolution crystal structures. Numerous efforts have been made in characterizing the peptide transporter (PepT1) and the apical sodium dependent bile acid transporter (ASBT) that are important for both their native transporter function as well as targets to increase absorption and act as therapeutic targets. In vitro and computational approaches have been applied to gain some insight into these transporters with some success. This represents an opportunity for optimizing molecules as substrates for the solute transporters and providing a further screening system for drug discovery. Clearly the future growth in knowledge of SLC function will be led by integrated in vitro and in silico approaches. |
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