Therapeutic peptidomimetics: targeting the undruggable space

Lloyd Mabonga, Priscilla Masamba, Abidemi Paul Kappo

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


The design of peptidomimetics, or modified peptides, has revolutionized the concept of drug discovery and attracted more attention and investment in integrating the fields of diagnostics and therapeutics. The importunity and peremptory need for synthesis and screening of synthetic biopolymers and their more stable modified derivatives are continuously increasing. Therapeutic peptidomimetics are a good example of synthetic mimicries whose pharmacophores mimic native proteins or peptides in three-dimensional space and retain the ability to modulate therapeutic vulnerabilities and produce desired pharmacological effects. Peptidomimetics are smart drugs designed to circumvent challenges associated with native peptides. They play an indispensable clinical and prognostic regulatory role in averting pathophysiological processes and disease progression. The design of peptide mimetics has expanded the biological understanding and therapeutic potential of protein–protein interactions (PPIs) in drug discovery technology. Over the years, PPIs have been regarded as intractable for drug discovery because of their highly dynamic and comprehensive interfacial areas. Nevertheless, advances in drug discovery technology have challenged scientists and prompted therapeutic interrogation of the widely overlooked “undruggable” space. New PPI network prognostic vulnerabilities have already been identified, with some potential drug-like candidates already on the market and in clinical trials. This chapter explores the quest to target therapeutic peptidomimetics as a tool to address the undruggable proteome in modern-day drug discovery.

Original languageEnglish
Title of host publicationPeptide and Peptidomimetic Therapeutics
Subtitle of host publicationFrom Bench to Bedside
Number of pages19
ISBN (Electronic)9780128201411
ISBN (Print)9780128204474
Publication statusPublished - 1 Jan 2022


  • Undruggable space
  • drug design
  • peptidomimetics
  • protein–protein interactions
  • therapeutic peptides

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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