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.