As mentioned above, a major limitation of most MPs is that they display poor passive membrane permeability, limiting their utility for engaging intracellular targets. The IP + motif is an interesting functional unit with respect to potentially influencing membrane permeability. It is relatively hydrophobic, especially in the case where quinoline or other more highly substituted P2CAs are employed to create the macrocycle, yet it carries a permanent positive charge (i.e., not due to a protonation event). It seems reasonable to hypothesize that the positive charge might concentrate the compound on the cell surface through electrostatic interactions and that the hydrophobic character of the heterocycle might stimulate movement across the membrane, resulting in improved passive membrane permeability.