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lüll The design of guanidinium-rich transporters and their internalization mechanisms Wender PA; Galliher WC; Goun EA; Jones LR; Pillow THAdv Drug Deliv Rev 2008[Mar]; 60 (4-5): 452-72The ability of a drug or probe to cross a biological barrier has historically been viewed to be a function of its intrinsic physical properties. This view has largely restricted drug design and selection to agents within a narrow log P range. Molecular transporters offer a strategy to circumvent these restrictions. In the case of guanidinium-rich transporters (GRTs), a typically highly water-soluble conjugate is found to readily pass through the non-polar membrane of a cell and for some across tissue barriers. This activity opens a field of opportunities for the use of GRTs to enable delivery of polar and non-polar drugs or probes as well as to enhance uptake of those of intermediate polarity. The field of transporter enabled or enhanced uptake has grown dramatically in the last decade. Some GRT drug conjugates have been advanced into clinical trials. This review will provide an overview of recent work pertinent to the design and mechanism of uptake of GRTs.|*Drug Design[MESH]|Animals[MESH]|Cell Membrane Permeability[MESH]|Cell Membrane/metabolism[MESH]|Drug Carriers/*chemistry[MESH]|Guanidine/*chemistry[MESH]|Humans[MESH]|Models, Biological[MESH]|Molecular Structure[MESH]|Pharmaceutical Preparations/administration & dosage/*chemistry/metabolism[MESH] |