Faculty Advisor or Committee Member

Dr. W. Grant McGimpsey, Advisor

Faculty Advisor or Committee Member

Dr. James P. Dittami

Identifier

etd-0428103-180827

Abstract

A series of bicyclic peptides have been designed and synthesized to provide ammonium ion complexation sites via hydrogen bonding in a tetrahedral geometry. Molecular modeling dynamics and electrostatics studies indicate that target compounds 1d-6d may provide better selectivity for ammonium ions over potassium ions than the ammonium ionophore currently used for blood analysis applications, nonactin. Attempts to synthesize 1d, cyclo(L-Glu1�D-Val2�L-Ala3�D-Lys4�D-Val5�L-Val6)-cyclo-(1ã-4å), were unsuccessful due to poor solubility of the synthetic intermediates. This led to the design of 2d-6d in which specific amino acid residues were chosen to provide higher solubility. Compound 2d, cyclo(L-Glu1�D-Ala2�D-Ala3�L-Lys4�D-Ala5�L-Ala6)-cyclo-(1ã-4å), was successfully synthesized, but was also too insoluble for characterization or testing in an ion selective electrode (ISE) sensor format. Compound 6d, cyclo(L-Glu1�D-Leu2�Aib3�L-Lys4�D-Leu5�D-Ala6)-cyclo-(1ã-4å), was successfully synthesized and characterized. When 6d was incorporated into an ISE sensor and tested as an ammonium ionophore, results indicated that the bicyclic peptide lacked solubility in the ISE membrane. A 13C-NMR study has been initiated in order to evaluate selectivity of 6d for ammonium over potassium and sodium cations in solution. Preliminary results with the potassium ionophore valinomycin as a control have been completed.

Publisher

Worcester Polytechnic Institute

Degree Name

MS

Department

Chemistry & Biochemistry

Project Type

Thesis

Date Accepted

2003-04-28

Accessibility

Unrestricted

Subjects

solution 13C-NMR study, solid phase peptide synthesis, bicyclic peptides, ammonium ionophores, valinomycin, ion selective electrode, Blood, Analysis, Peptides, Synthesis, Ionophores, Electrodes, Ion selective

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