Designing peptide-based scaffolds as drug delivery vehicles.
Methods for delivering drugs into cells remain an important part of the process of designing drugs. One promising approach is the concept of loligomers, synthetic peptides composed of a branched polylysine core harboring identical arms. Loligomers are typically synthesized with eight arms, each carrying peptide signals guiding their import and localization into cells. The most important advantage of loligomers is the multivalent presentation of targeting signals resulting from a tentacular arrangement. Multivalency increases the efficiency of import and intracellular routing signals as compared to similar linear peptides. Secondly, it reduces and delays the impact of peptide degradation in terms of cellular processing and compartmentalization. The vectorial delivery of nucleus-directed loligomers into cells has recently been confirmed by microscopy and flow cytometry studies. Practical uses of loligomers as intracellular vehicles include the import of plasmid DNA into cells, the conjugation of chemical groups, such as photosensitizers for use in photodynamic therapy, and the incorporation of cytotoxic T-lymphocyte (CTL) epitopes with a view to creating synthetic vaccines. Branched peptides such as loligomers represent simple and versatile molecular vehicles with potential applications in a wide variety of drug design approaches.
Brokx
Richard D
RD
Department of Medical Biophysics, University of Toronto, 610 University Avenue, Ont., M5G 2M9, Toronto, Canada.
Bisland
Stuart K
SK
Gariépy
Jean
J
D016503:Drug Delivery Systems; D015195:Drug Design; D022761:Gene Transfer, Horizontal; D006801:Humans; D010455:Peptides / Q000008:administration & dosage*; D010778:Photochemotherapy; D014612:Vaccines / Q000008:administration & dosage
D010455:Peptides; D014612:Vaccines