β-Amino Acids: Versatile Peptidomimetics

Author(s): David L. Steer, Rebecca A. Lew, Patrick Perlmutter, A. Ian Smith, Marie-Isabel Aguilar.

Journal Name: Current Medicinal Chemistry

Volume 9 , Issue 8 , 2002

Become EABM
Become Reviewer

Abstract:

The use of peptidomimetics has emerged as a powerful means for overcoming the limitations inherent in the physical characteristics of peptides thus improving their therapeutic potential. A peptidomimetic approach that has emerged in recent years with significant potential, is the use of β-amino acids. β-Amino acids are similar to α-amino acids in that they contain an amino terminus and a carboxyl terminus. However, in β-amino acids two carbon atoms separate these functional termini. β-amino acids, with a specific side chain, can exist as the R or S isomers at either the α (C2) carbon or the β (C3) carbon. This results in a total of 4 possible diastereoisomers for any given side chain. The flexibility to generate a vast range of stereo- and regioisomers, together with the possibility of disubstitution, significantly expands the structural diversity of β-amino acids thereby providing enormous scope for molecular design. The incorporation of β-amino acids has been successful in creating peptidomimetics that not only have potent biological activity, but are also resistant to proteolysis. This article reviews the rapidly expanding applications of β-amino acids in the design of bioactive peptide analogues ranging from receptor agonists and antagonists, MHC-binding peptides, antimicrobial peptides and peptidase inhibitors. Given their structural diversity taken together with the ease of synthesis and incorporation into peptide sequences using standard solid-phase peptide synthesis techniques, β-amino acids have the potential to form a new platform technology for peptidomimetic design and synthesis.

Keywords: amino acids, sandostatin, mhc-binding peptides, dna-binding peptides, bioactive foldamers

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 9
ISSUE: 8
Year: 2002
Page: [811 - 822]
Pages: 12
DOI: 10.2174/0929867024606759
Price: $58

Article Metrics

PDF: 29