Date of Award

Fall 1995

Document Type

Thesis

Degree Name

Master of Science in Applied Chemistry - (M.S.)

Department

Chemical Engineering, Chemistry and Environmental Science

First Advisor

Carol A. Venanzi

Second Advisor

Tamara M. Gund

Third Advisor

Barbara B. Kebbekus

Abstract

Accurate molecular models were constructed by a rapid prototyping process, called stereolithography. This process uses a computer-controlled laser to cure and solidify a photosensitive liquid polymer. Using a computer-aided design (CAD) program, spheres of appropriate van der Waals or CPK radii were drawn and placed in the three dimensional CAD space, in accordance with the atomic coordinates obtained from quantum mechanical calculations and from neutron diffraction data. These design data were used to drive the stereolithography system where the models were built in the same shape as the CAD image. The models built for the purpose of this work consisted of three amino acids and two structural analogs used in the study of the L-alanine taste receptor of the channel catfish, as well as the enzyme mimic β-cyclodextrin along with the transition state for the cleavage of phenyl acetate by the 2' and 3' hydroxyl oxygens of β-cyclodextrin. Models of the drug amiloride, as well as two analogs of this compound were also constructed. These compounds were used in the study of the epithelial Na+ channel.

Nuclear Magnetic Resonance spectroscopy was applied to the compounds amiloride hydrochloride and amiloride free base. Data generated with this methodology is useful in determining the conformations of these compounds in solution and for comparison with the results of theoretical calculations done in this laboratory. Models of the structures determined in this way can give a better approximation of the electrostatic and steric requirements necessary for the drug to bind with the receptor.

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