General inverse solid-phase synthesis method for C-terminally modified peptide mimetics.
Peptide mimetics are of considerable interest as bioactive agents and drugs. C-terminally modified peptide mimetics are of particular interest given the synthetic versatility of the carboxyl group and its derivatives. A general approach to C-terminally modified peptide mimetics, based on a urethane attachment strategy and amino acid t-butyl ester-based N-to-C peptide synthesis, is described. This approach is compatible with the reaction conditions generally employed for solution-phase peptide mimetic synthesis. To develop and demonstrate this approach, it was employed for the solid-phase synthesis of peptide trifluoromethyl ketones, peptide boronic acids, and peptide hydroxamic acids. The development of a versatile general approach to C-terminally modified peptides using readily available starting materials provides a basis for the combinatorial and parallel solid-phase synthesis of these peptide mimetic classes for bioactive agent screening and also provides a basis for the further development of solid-phase C-terminal functional group elaboration strategies.
Sasubilli
Ramakrishna
R
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110, USA.
Gutheil
William G
WG
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004952:Esters / Q000737:chemistry; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
D000596:Amino Acids; D004952:Esters; D019151:Peptide Library; D010455:Peptides