Dendritic Guanidines as Efficient Analogues of Cell Penetrating Peptides

Colin V Bonduelle; Elizabeth R Gillies

doi:10.3390/ph3030636

Dendritic Guanidines as Efficient Analogues of Cell Penetrating Peptides

Pharmaceuticals (Basel). 2010 Mar 12;3(3):636-666. doi: 10.3390/ph3030636.

Authors

Colin V Bonduelle¹, Elizabeth R Gillies^{2

3}

Affiliations

¹ Department of Chemistry, The University of Western Ontario, 1151 Richmond St., London, N6A 5B7, Canada.
² Department of Chemistry, The University of Western Ontario, 1151 Richmond St., London, N6A 5B7, Canada. egillie@uwo.ca.
³ Department of Chemical and Biochemical Engineering, The University of Western Ontario, 1151 Richmond St., London, N6A 5B9, Canada. egillie@uwo.ca.

Abstract

The widespread application of cell penetrating agents to clinical therapeutics and imaging agents relies on the ability to prepare them on a large scale and to readily conjugate them to their cargos. Dendritic analogues of cell penetrating peptides, with multiple guanidine groups on their peripheries offer advantages as their high symmetry allows them to be efficiently synthesized, while orthogonal functionalities at their focal points allow them to be conjugated to cargo using simple synthetic methods. Their chemical structures and properties are also highly tunable as their flexibility and the number of guanidine groups can be tuned by altering the dendritic backbone or the linkages to the guanidine groups. This review describes the development of cell-penetrating dendrimers based on several different backbones, their structure-property relationships, and comparisons of their efficacies with those of known cell penetrating peptides. The toxicities of these dendritic guanidines are also reported as well as their application towards the intracellular delivery of biologically significant cargos including proteins and nanoparticles.

Keywords: cell penetrating peptide; cell-uptake; dendrimer; drug delivery; guanidine; toxicity.

Publication types

Review