A general approach to modular, allosteric chemosensors is described. Chemosensors are small synthetic molecules which produces a visible signal upon interaction with a specific analyte. In the biochemical community, they have been used as sensitive, non-destructive methods for quantifying the amount of a particular analyte in cells. Chemosensors have played a pivotal role in unraveling the cellular function of a number of metal ions, most notably cell calcium. Similar sensors for organic molecules have not reached this level of success.
The specific aims of this research are to develop a novel chemosensor framework and subsequently apply it to two specific problems. The first problem is the recognition of amino acids in aqueous solution. This is an important unsolved problem with broad ramifications. Specifically, excitatory amino acids will be targeted. This work will have direct impact on neurochemical research in that it is currently difficult to directly detect neurotransmitters such as glutamate in a non-destructive manner. Chemosensors for these molecules will enable a great deal of basic research into neurotransmission. The second specific target is a chemosensor for the redox potential present inside of cells. Since it has recently been suggested that a number of cell processes are controlled by the cellular redox potential, knowledge of this potential is of great importance. Sensors which can quickly and easily quantify the cellular reduction potential would be invaluable for work on the mechanisms of these processes.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Medicinal Chemistry Study Section (MCHA)
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Preusch, Peter C
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Avetta, Christopher T; Shorthill, Berkeley J; Ren, Chun et al. (2012) Molecular tubes for lipid sensing: tube conformations control analyte selectivity and fluorescent response. J Org Chem 77:851-7
Zhang, Shaohui; Glass, Timothy E (2010) An indicator displacement assay with independent dual wavelength emission. Tetrahedron Lett 51:112-114
Dalgarno, Scott J; Claudio-Bosque, Karla M; Warren, John E et al. (2008) Interpenetrated nano-capsule networks based on the alkali metal assisted assembly of p-carboxylatocalix[4]arene-O-methyl ether. Chem Commun (Camb) :1410-2
Plante, Jeffrey P; Glass, Timothy E (2006) Shape-selective fluorescent sensing ensemble using a tweezer-type metalloreceptor. Org Lett 8:2163-6
Shorthill, Berkeley J; Avetta, Christopher T; Glass, Timothy E (2004) Shape-selective sensing of lipids in aqueous solution by a designed fluorescent molecular tube. J Am Chem Soc 126:12732-3
Secor, Kristen E; Glass, Timothy E (2004) Selective amine recognition: development of a chemosensor for dopamine and norepinephrine. Org Lett 6:3727-30
Feuster, Ellen K; Glass, Timothy E (2003) Detection of amines and unprotected amino acids in aqueous conditions by formation of highly fluorescent iminium ions. J Am Chem Soc 125:16174-5
Shorthill, Berkeley J; Granucci, Robert G; Powell, Douglas R et al. (2002) Synthesis of 3,5- and 3,6-linked calix[n]naphthalenes. J Org Chem 67:904-9
Raker, Joseph; Glass, Timothy E (2002) Selectivity via cooperative interactions: detection of dicarboxylates in water by a pinwheel chemosensor. J Org Chem 67:6113-6
Raker, J; Glass, T E (2001) Cooperative ratiometric chemosensors: pinwheel receptors with an integrated fluorescence system. J Org Chem 66:6505-12