The Multifaceted Role of Glycosaminoglycans in the Cellular Uptake of Cell-Penetrating Peptides

R. Wallbrecher1, S. Schmidt1, W. P. Verdurmen1, P. H. Bovee-Geurts1, F. Broecker2,3, A. Reinhardt2,3, T. H. van Kuppevelt1, J. Eilander1, S. Fanghänel4, J. Bürck5, P. Wadhwani5, P. H. Seeberger2,3, A. S. Ulrich4,5, R. Brock1

1Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University
Medical Centre, 6525 GA Nijmegen, the Netherlands; 2Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, 14476 Potsdam, Germany; 3Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany; 4Karlsruhe Institute of Technology (KIT), Institute for Organic Chemistry and CFN, 76131 Karlsruhe, Germany; 5KIT, Institute for Biological Interfaces (IBG-2), 76021 Karlsruhe, Germany


Here, we demonstrate that in spite of a general propensity to interact with CPPs the role of GAG in uptake varies greatly and depends on the nature of the CPP. For variants of a CPP derived from the human lactoferrin protein there was a negative correlation of the stoichiometry of GAG binding and uptake, indicating that GAG clustering promoted uptake. This CPP shares characteristics with other arginine rich CPP such as nonaarginine. In contrast, for analogs of the amphipathic transportan 10 (TP10) clustering impeded uptake. To monitor GAG clustering in living cells, metabolic labeling of sugars was employed. Here, cells are incubated with azido-bearing sugar analogs. Following incorporation into sialic acids, fluorescent labels can be introduced by click chemistry

© Copyright Controlled Release Society  | Contact Us - Report a Bad Link |
Admin Access