City Research Online

Abstract

A series of conformational studies on Y-aminobutyric acid (GABA) and its agonists B-guanidino propionic acid (gGP) and muscimol are reported.

The development of a library of computer programs for carrying out the necessary calculations is described. The crystal structures of GABA.HC{, GABA and #GP are reported. GABA is found to be partially folded in the pure crystal form, but fully-extended in the crystalline hydrochloride. §GP is found to be folded in the crystalline state.

The results of CNDO/2 calculations on GABA, 8GP and muscimol are given. Fully—-folded conformations are predicted to be strongly favoured for the isolated zwitterions of GABA and 8GP, while the muscimol molecule is found to prefer a planar conformation. CNDO/2 calculations on bicuculline, a specific competitive antagonist of GABA, are also reported. Similarities in the electronic structures of bicuculline and the three agonists are noted.

A series of classical energy calculations on GABA and GP are described. These predict fully-folded conformers as the lowest energy rotamers for the isolated zwitterions of the two molecules.

The various sets of conformational data available on GABA, BGP, and muscimol are discussed. In particular, isolated forms of GABA are found to favour fully-folded conformations, but it is noted that the effect of the environment is significant: a more-extended conformer of GABA is found in the solid state. Extended conformers of GABA are also likely to exist in solution.

The results from the crystal structure studies and the energy calculations, together with other published data, are used in a discussion of the pharmacological activity of GABA, GP, muscimol and bicuculline. Possible similarities in charge distributions are elucidated.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science Q Science > QC Physics Q Science > QD Chemistry
Departments:	School of Science & Technology School of Science & Technology > School of Science & Technology Doctoral Theses Doctoral Theses

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