Molecular structural requirements for binding and activation of L-alanine taste receptors |
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Authors: | B. P. Bryant K. Leftheris J. V. Quinn J. G. Brand |
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Affiliation: | (1) Monell Chemical Senses Center, 3500 Market Street, 19104 Philadelphia, PA, USA;(2) Department of Biochemistry, School of Dental Medicine, University of Pennsylvania and Veterans Affairs Medical Center, Philadelphia, USA;(3) Present address: Bristol-Myers Squibb Pharmaceutical Research Institute, 675 College Road, E., 08540 Princeton, NJ, USA |
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Abstract: | Summary L-Alanine binds to and activates specific taste receptors ofIctalurus punctatus, the channel catfish. In order to determine the structural requirements for receptor binding and activation in this model system, a number of analogues of L-alanine were tested using a neurophysiological assay and a competitive ligand binding assay. These assays measured the ability of analogues to activate taste receptors and to displace L-[3H]alanine from L-alanine binding sites. Of those derivatives with modifications of the sidechain, L-serine, glycine,-chloro-L-alanine and 1-amino-cyclopropane-1-carboxylic acid were the most potent analogues with IC50s similar to and neural responses slightly decremented from that of L-alanine. Derivatives containing branched sidechains or sidechains of otherwise increased volume were considerably less active. All modifications of the-carboxylic acid and the-amine, including amides, esters and various isosteres, led to substantial reduction in the analogues' ability to displace L-[3H]alanine and, in most cases, very weak stimulatory capability. However, L-lactic acid was a reasonably strong stimulus, but a poor competitor, suggesting that it acts at a different receptor site. Overall, these results indicate the importance of the charged amine and carboxylic acid groups for binding to and activation of the receptor for L-alanine. Moreover, modifications around the chiral center of L-alanine support the hypothesis that receptor binding and activation are separate processes in this model taste system. |
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Keywords: | Amino acids Structure/activity L-Alanine Taste receptor L-Alanine analogues Ligand binding assay |
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