An overview of peptide and peptoid foldamers in medicinal chemistry.
BACKGROUND
Foldamers are artificial self-organizing systems with various critical properties: i) a stable and designable secondary structure; ii) a larger molecular surface as compared with ordinary organic drug molecules; iii) appropriate control of the orientation of the side-chain functional groups; iv) resistance against proteolytic degradation, which leads to potentially increased oral bioavailability and a longer serum half-life relative to ordinary α-peptides; and v) the lower conformational freedom may result in increased receptor binding in comparison with the natural analogs.


METHODS
This article covers the general properties and types of foldamers. This includes highlighted examples of medicinal chemical applications, including antibacterial and cargo molecules, anti-Alzheimer compounds and protein-protein interaction modifiers.


CONCLUSIONS
Various new foldamers have been created with a range of structures and biological applications. Membrane-acting antibacterial foldamers have been introduced. A general property of these structures is their amphiphilic nature. The amphiphilicity can be stationary or induced by the membrane binding. Cell-penetrating foldamers have been described which serve as cargo molecules, and foldamers have been used as autophagy inducers. Anti-Alzheimer compounds too have been created and the greatest breakthrough was attained via the modification of protein-protein interactions. This can serve as the chemical and pharmaceutical basis for the relevance of foldamers in the future.
István M
IM
Mándity
a University of Szeged Institute of Pharmaceutical Chemistry , H-6720 Szeged, Eötvös u. 6, Hungary +36 62 545 768 ; +36 62 545 564 ; +36 62 545 705 ; mandity@pharm.u-szeged.hu ; fulop@pharm.u-szeged.hu.
Ferenc
F
Fülöp
D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D034444:Peptoids / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
D010455:Peptides; D034444:Peptoids
antibacterial; arylamide foldamer; helix; medicinal chemical application; peptoid; protein–protein interaction; strand; β-peptide