A Diaminodiacid (DADA) Strategy for the Development of Disulfide Surrogate Peptides

Chem Asian J. 2020 Sep 15;15(18):2793-2802. doi: 10.1002/asia.202000609. Epub 2020 Aug 11.

Abstract

Disulfide bond-containing peptides are useful molecular scaffolds with diagnostic and therapeutic applications due to their good biological activity and good target selectivity, but their utility is sometimes limited by the lability of the disulfide moiety under reducing conditions and in the presence of disulfide bond isomerase. The development of disulfide surrogates with improved redox stability has been an area of ongoing research; and one possible strategy is based on a diaminodiacid (DADA) moiety, which can be used to synthesize the disulfide bond replacement peptides with precise structures and enhanced stability through automated solid-phase peptide synthesis (SPPS). This review summarizes recent developments in the DADA-based SPPS of peptide disulfide surrogates. Some representative applications and structural studies on the DADA-based disulfide surrogates are described.

Keywords: diaminodiacid; disulfide; disulfide bond; disulfide surrogate peptide; solid-phase peptide synthesis.

Publication types

  • Review

MeSH terms

  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry
  • Cyclization
  • DNA-Binding Proteins / chemical synthesis
  • DNA-Binding Proteins / chemistry
  • Disulfides / chemistry*
  • Hydrocarbons / chemistry
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Solid-Phase Synthesis Techniques

Substances

  • Antimicrobial Cationic Peptides
  • DNA-Binding Proteins
  • Disulfides
  • Hydrocarbons
  • Peptides
  • Peptides, Cyclic
  • tachyplesin peptide, Tachypleus tridentatus