Understanding renal transport mechanisms is essential to predicting molecular interactions and targeting drugs to specific transporters. This study focuses on characterizing rbOAT1 and rbOAT3 with respect to interactions with compounds that varied in charge, length and hydrophobicity. Straight chain dicarboxylates of five carbons or more inhibited both transporters well. Maximum inhibition occurred with glutarate (5C). Monocarboxylates interacted poorly with both transporters, yet exhibited greater inhibition as the chain length increased. Aromatic dicarboxylates inhibited both transporters optimally at a charge separation similar to that of glutarate. Both OAT1 and OAT3 were inhibited by reduced and oxidized 2,3-dimercapto-1-propane sulfonate (DMPS). To test the chemical properties of DMPS that facilitated its interaction with rbOAT1 and rbOAT3, I used 3-mercapto-1-propane sulfonate and found that the SH groups are essential in stabilizing DMPS to the binding sites. These results indicate that the size, hydrophobicity, charge, and H-bonding capabilities of a molecule work together to stabilize it to the transporter binding site.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/292037 |
| Date | January 2003 |
| Creators | Munoz, Lynn D. |
| Contributors | Wright, Steve H. |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | en_US |
| Detected Language | English |
| Type | text, Thesis-Reproduction (electronic) |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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