R.Wallbrecher1, W.P.R. Verdurmen1, P.H. Bovee-Geurts1, F. Bröcker2, A. Reinhardt2, P.H. Seeberger2, R. Brock1
1Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, the Netherlands 2Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Arnimallee 22, 14195 Berlin, Germany
A detailed structure-activity relationship regarding the correlation between the binding characteristics of the interaction between heparan sulfate (HS) and a cell-penetrating peptide (CPP) derived from human lactoferrin (hLF) is described. The number of arginine residues was the major factor determining the binding affinity and internalization of the tested CPPs. Uptake negatively correlated with stoichiometry, a finding which suggests that HS acts as a buffer thereby impeding uptake.