Boc-allo-Ile-OH

De novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties not precedented in nature. The success relies heavily on the ability to design relatively short peptides that can espouse stable secondary structures. To this end, substitution with α,β-didehydroamino acids, especially α,β-didehydrophenylalanine (Δ(z)Phe), comes in use for spawning well-defined structural motifs. Introduction of ΔPhe induces β-bends in small and 3(10)-helices in longer peptide sequences. The present work aims to investigate the effect of nature and the number of amino acids interspersed between two ΔPhe residues in two model undecapeptides, Ac-Gly-Ala-ΔPhe-Ile-Val-ΔPhe-Ile-Val-ΔPhe-Ala-Gly-NH(2) (I) and Boc-Val-ΔPhe-Phe-Ala-Phe-ΔPhe-Phe-Leu-Ala-ΔPhe-Gly-OMe (II). Peptide I was synthesized using solid-phase chemistry and characterized using circular dichroism spectroscopy. Peptide II was synthesized using solution-phase chemistry and characterized using circular dichroism and nuclear magnetic resonance spectroscopy. Peptide I was designed to examine the effect of incorporating β-strand-favoring residues like valine and isoleucine as spacers between two ΔPhe residues on the final conformation of the resulting peptide. Circular dichroism studies on this peptide have shown the existence of a 3(10)-helical conformation. Peptide II possesses three amino acids as spacers between ΔPhe residues and has been reported to adopt a mixed 3(10)/α-helical conformation using circular dichroism and nuclear magnetic resonance spectroscopy studies.

Glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), phenylalanine (Phe), and lysine (Lys) esters of metronidazole were synthesized using dicyclohexylcarbodiimide (DCC) coupling or a mixed-anhydride route, using tert-butyloxycarbonyl (tert-Boc) amino acids. Human serum-catalyzed hydrolysis of these esters at 37 degrees C give half-lives varying from 4.5 min for the Phe ester to 96 h for the Ile ester. Also determined was the pH-rate profile for hydrolysis in aqueous buffers at 25 degrees C. A linear relationship was observed between the logarithmic value of the hydrolysis rate constant in serum and that of the OH- -catalyzed hydrolysis of cationic esters. This finding may indicate that the esters studied are "equally" poor substrates for binding to the enzymes in serum and, thus, the difference observed in the serum-catalyzed hydrolysis rate is solely derived from the chemical lability of an ester bond. Interestingly, the extent of chemical activation observed in the buffer system appears to be amplified in the serum-catalyzed hydrolysis.