Michael Kahn

Methodology for the synthesis of mimetics of peptide β-turns

Abstract This letter describes a scenario which provides for the stereospecific introduction of both the amino and carboxyl termini portion of a designed β-turn mimetic.

Design, synthesis and conformational analysis of γ-turn peptide mimetics of bradykinin

Abstract Gamma-turns are regular secondary structure elements, found with some frequency in small peptides, that have been implicated in the biologically active conformations of several systems. This report describes the design, synthesis and conformational analysis of a non-peptide γ-turn mimetic. Low energy conformations of the mimetic system exhibit good conformational agreement with an experimentally observed peptide γ-turn. The mimetics were incorporated into the nonapeptide bradykinin, for which a γ-turn, formed by residues Ser 6 to Phe 8, has been hypothesized to be a bioactive conformation. The results indicate that a bioactive conformation of bradykinin may include a reverse turn at this position.

The design and synthesis of a nonpeptide mimic of an immunosuppressing peptide

Abstract The synthesis and preliminary biological evaluation of a nonpeptide mimic of the immunosuppressant tripeptide (Lys-Pro-Arg) is described.

The incorporation of β-turn prosthetic units into merrifield solid phase peptide synthesis

Abstract The incorporation of designed conformationally restricted nonpeptide β-turn prosthetic units onto the amino terminus of peptides is discussed. The synthesis of the peptides, including the incorporation of the β-turn mimetic was accomplished using Merrifield solid phase automated peptide synthesis.

Nonpeptide β-turn mimetics of enkephalin

Abstract The design and synthesis of a conformationally restricted peptide mimetic of the endogenous opiate peptide leucine enkephalin is described. This mimetic incorporates a nonpeptide β-turn prosthetic unit; conformational analysis indicates that the active isomer exhibits a conformation closely corresponding to that of a highly potent, β-selective enkephalin analog. Tyr- d -Pen-Gly-Phe- d -Pen (DPDPE, Pen=Penicillamine). Preliminary pharmacological investigation indicated that one isomer of the mimetic species exhibits significant in vivo analgesic activity, despite relatively low in vitro binding affinity.

Design and synthesis of hypertrehalosemic hormoe mimetics

Abstract Hypertrehalosemic hormoe (HTH) is an insect neurohormone isolated from the tropical cockroach, Blaberus discoidalis. To examin the hypothesis that the bioactive conformation of HTH contains a β-turn, we have designed, synthesized and evaluated a first generation HTH analog incorporating a conformationally restricted β-turn mimetic. Conformational and biological evaluation indicates that an isomer closely approximately a type II β-turn exhibits limited biological activity, while isomers with extended conformations exhibit no activity, providing evidence for the turn hypothesis.

Enantiospecific routes to 3,4 disubstituted azetidinones

Abstract Enantiospecific routes to 3,4 disubstituted azetidinones are outlined which commence with readily available β-ketoester precursors.