Recent Advances in the Synthesis and Applications of Reduced Amide Pseudopeptides

Matej      Zivec; Ziga      Jakopin; Stanislav      Gobec

Abstract

Being one of the simplest and widely used isosteric replacements for the peptide bond, reduced amide has been successfully applied in the synthesis of many bioactive compounds. The introduction of reduced amide not only confers the pseudopeptide a higher enzymatic resistance and a linear and more flexible structure, but also increases its hydrophylicity due to the introduction of a protonable group. It has also proved adequate as a transition state mimetic for the tetrahedral intermediate formed during the hydrolysis of the peptide bond. Recent advances in the solution and solid-phase synthesis of reduced amides that emerged during the past ten years are presented. Most of them include the use of microwave irradiation to shorten the reaction times and improve the yields. The bioorganic chemistry of reduced-peptide-containing compounds represents an area of growing interest and it has recently been expanded to include analogues of endogenous peptides/ hormones that are resistant to hydrolysis by serum peptidases and enzyme inhibitors. Under certain conditions, synthetic peptides are highly immunogenic in animals, and might constitute chemically defined, safe and cheap vaccines. Linear pseudooligolysines, containing multiple adjacent CH2NH amide bond are potential candidates for future use as DNA carriers in gene delivery. Reduced amides have also seen use in the preparation of peptide nucleic acids and antibacterial peptides.

Keywords: Reduced peptide bond, peptidomimetics, peptide analogues, vaccines, enzyme inhibitors, synthesis

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