| Abstract | The solution-phase structures of a number of conformationally restricted gamma-aminobutyric acid (GABA) analogues are investigated at the MP2/6-31+G* level of theory, using both explicit water molecules and the conductor-like screening solvation model (COSMO) to model solvation. GABA analogues constrained in a cis conformation by either a double bond or cyclopropane ring have the potential to attain either folded, intramolecularly hydrogen-bonded, or partially folded conformations in solution. Systems constrained in a cis conformation by a cyclopentane or cyclopentene ring are more conformationally restricted and exist only in a folded, intramolecularly hydrogen-bonded form. GABA analogues constrained in a trans conformation by either a double bond or cyclopropane ring have the potential to adopt either partially folded or fully extended conformations in solution. Due to a lack of conformational flexibility, analogues that are constrained in a trans conformation by a cyclopentane or cyclopentene ring attain only partially folded conformations. Like GABA, conformationally flexible GABA analogues possess a large number of stable rotamers, and may exist in any or all of these conformations in aqueous solution. The structures of these analogues provide an essential foundation for subsequent structure-activity analysis of ligand binding at GABA receptors and transporters. This work is therefore expected to facilitate the design and development of new biologically active GABA analogues to treat GABA-related neurological disorders. |
| Authors | Deborah L Crittenden, Mary Chebib, Meredith J T Jordan
(Affiliation: School of Chemistry, University of Sydney, NSW, Australia 2006.)
|
| Journal | The journal of physical chemistry. A
(J Phys Chem A)
Vol. 109
Issue 18
Pg. 4195-201
(May 12 2005)
ISSN: 1089-5639 United States |
| PMID | 16833745
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Ions
- Solutions
- gamma-Aminobutyric Acid
|
| Topics |
- Ions
(chemistry)
- Solutions
- gamma-Aminobutyric Acid
(analogs & derivatives, chemistry)
|
