The application of Freidinger lactams and their analogs in the design of conformationally constrained peptidomimetics

Curr Med Chem. 2006;13(13):1525-56. doi: 10.2174/092986706777442066.

Abstract

Peptides exist in solution as an equilibrium mixture of conformers. The backbone conformational constraints are of interest as a means of limiting degrees of freedom and thereby constraining a synthetic peptide into the bioactive conformation. This concept plays an important role in the design of peptidomimetics in the drug development process. In the early eighties, Freidinger proposed the concept of protected lactam-bridged dipeptides, which was a milestone in the design of conformationally constrained peptides. These types of compounds, now widely known as Freidinger lactams, have been of interest to many medicinal and peptide chemists. This review seeks to present the various applications that Freidinger lactams and their hetero-, fused- and unsaturated analogs have found in the design of conformationally constrained peptidomimetics in different therapeutic areas.

Publication types

  • Review

MeSH terms

  • Angiotensin II / antagonists & inhibitors
  • Biochemistry / methods
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Factor Xa Inhibitors
  • Humans
  • Lactams / chemistry*
  • Leukocyte Elastase / antagonists & inhibitors
  • Molecular Conformation
  • Molecular Mimicry*
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Protein Conformation
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins / chemistry
  • Proteins / pharmacology
  • Renin / antagonists & inhibitors
  • Renin-Angiotensin System / drug effects
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Thrombin / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • Factor Xa Inhibitors
  • Lactams
  • Peptides
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Serine Proteinase Inhibitors
  • Angiotensin II
  • Leukocyte Elastase
  • Thrombin
  • Renin