In Chemistry

ii 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-(1γ-4ε), 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-(1γ-4ε), 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-(1γ-4ε), was successfully synthesized and characterized. When 6d was incorporated into an IS