title: Beta-amino acids: versatile peptidomimetics.
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 beta-amino acids. Beta-amino acids are similar to alpha-amino acids in that they contain an amino terminus and a carboxyl terminus. However, in beta-amino acids two carbon atoms separate these functional termini. beta-amino acids, with a specific side chain, can exist as the R or S isomers at either the alpha (C2) carbon or the beta (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 beta-amino acids thereby providing enormous scope for molecular design. The incorporation of beta-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 beta-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, beta-amino acids have the potential to form a new platform technology for peptidomimetic design and synthesis.
authors.affiliation: Department of Biochemistry & Molecular Biology, Monash University, Monash, Vic 3800, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Steer
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Lew
authors.forename: Patrick
authors.initials: P
authors.lastname: Perlmutter
authors.forename: A Ian
authors.initials: AI
authors.lastname: Smith
authors.forename: Marie-Isabel
authors.initials: MI
authors.lastname: Aguilar
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D010455:Peptides