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• W2085065303 abstract "All living systems require biochemical barriers. As a consequence, all drugs, imaging agents, and probes have targets that are either on, in, or inside of these barriers. Fifteen years ago, we initiated research directed at more fully understanding these barriers and at developing tools and strategies for breaching them that could be of use in basic research, imaging, diagnostics, and medicine. At the outset of this research and now to a lesser extent, the rules for drug design biased the selection of drug candidates mainly to those with an intermediate and narrow log P. At the same time, it was becoming increasingly apparent that Nature had long ago developed clever strategies to circumvent these rules. In 1988, for example, independent reports documented the otherwise uncommon passage of a protein (HIV-Tat) across a membrane. A subsequent study implicated a highly basic domain in this protein (Tat49-57) in its cellular entry. This conspicuously contradictory behavior of a polar, highly charged peptide passing through a nonpolar membrane set the stage for learning how Nature had gotten around the current rules of transport. As elaborated in our studies and discussed in this Account, the key strategy used in Nature rests in part on the ability of a molecule to change its properties as a function of microenvironment; such molecules need to be polarity chameleons, polar in a polar milieu and relatively nonpolar in a nonpolar environment. Because this research originated in part with the protein Tat and its basic peptide domain, Tat49-57, the field focused heavily on peptides, even limiting its nomenclature to names such as cell-penetrating peptides, cell-permeating peptides, protein transduction domains, and membrane translocating peptides. Starting in 1997, through a systematic reverse engineering approach, we established that the ability of Tat49-57 to enter cells is not a function of its peptide backbone, but rather a function of the number and spatial array of its guanidinium groups. These function-oriented studies enabled us and others to design more effective peptidic agents and to think beyond the confines of peptidic systems to new and even more effective nonpeptidic agents. Because the function of passage across a cell membrane is not limited to or even best achieved with the peptide backbone, we referred to these agents by their shared function, cell-penetrating molecular transporters. The scope of this molecular approach to breaching biochemical barriers has expanded remarkably in the past 15 years: enabling or enhancing the delivery of a wide range of cargos into cells and across other biochemical barriers, creating new tools for research, imaging, and diagnostics, and introducing new therapies into clinical trials." @default.
• W2085065303 created "2016-06-24" @default.
• W2085065303 creator A5006480688 @default.
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• W2085065303 date "2013-05-22" @default.
• W2085065303 modified "2023-10-10" @default.
• W2085065303 title "Fifteen Years of Cell-Penetrating, Guanidinium-Rich Molecular Transporters: Basic Science, Research Tools, and Clinical Applications" @default.
• W2085065303 cites W1505612226 @default.
• W2085065303 cites W1590085201 @default.
• W2085065303 cites W1963633899 @default.
• W2085065303 cites W1963819255 @default.
• W2085065303 cites W1968248620 @default.
• W2085065303 cites W1969217480 @default.
• W2085065303 cites W1976659952 @default.
• W2085065303 cites W1977943274 @default.
• W2085065303 cites W1978498174 @default.
• W2085065303 cites W1985164165 @default.
• W2085065303 cites W1988812196 @default.
• W2085065303 cites W1989772178 @default.
• W2085065303 cites W1991037959 @default.
• W2085065303 cites W1991830829 @default.
• W2085065303 cites W1994272486 @default.
• W2085065303 cites W2004335248 @default.
• W2085065303 cites W2011886949 @default.
• W2085065303 cites W2012596484 @default.
• W2085065303 cites W2018682207 @default.
• W2085065303 cites W2020316252 @default.
• W2085065303 cites W2021199155 @default.
• W2085065303 cites W2022163459 @default.
• W2085065303 cites W2024128913 @default.
• W2085065303 cites W2027633428 @default.
• W2085065303 cites W2029346749 @default.
• W2085065303 cites W2029766213 @default.
• W2085065303 cites W2030254243 @default.
• W2085065303 cites W2031804169 @default.
• W2085065303 cites W2032250529 @default.
• W2085065303 cites W2033191256 @default.
• W2085065303 cites W2034414337 @default.
• W2085065303 cites W2037695759 @default.
• W2085065303 cites W2040078811 @default.
• W2085065303 cites W2040885207 @default.
• W2085065303 cites W2042143995 @default.
• W2085065303 cites W2043195487 @default.
• W2085065303 cites W2066848489 @default.
• W2085065303 cites W2069244797 @default.
• W2085065303 cites W2070693578 @default.
• W2085065303 cites W2075231390 @default.
• W2085065303 cites W2076403704 @default.
• W2085065303 cites W2076859770 @default.
• W2085065303 cites W2079335891 @default.
• W2085065303 cites W2080660363 @default.
• W2085065303 cites W2087094217 @default.
• W2085065303 cites W2089954377 @default.
• W2085065303 cites W2094202171 @default.
• W2085065303 cites W2094492208 @default.
• W2085065303 cites W2094787420 @default.
• W2085065303 cites W2099132605 @default.
• W2085065303 cites W2103119315 @default.
• W2085065303 cites W2105668301 @default.
• W2085065303 cites W2111994795 @default.
• W2085065303 cites W2118838144 @default.
• W2085065303 cites W2122437201 @default.
• W2085065303 cites W2123650819 @default.
• W2085065303 cites W2126488413 @default.
• W2085065303 cites W2129453116 @default.
• W2085065303 cites W2144042477 @default.
• W2085065303 cites W2144074878 @default.
• W2085065303 cites W2152483372 @default.
• W2085065303 cites W2160969819 @default.
• W2085065303 cites W2165186006 @default.
• W2085065303 cites W2172025448 @default.
• W2085065303 cites W2614480585 @default.
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• W2085065303 doi "https://doi.org/10.1021/ar4000554" @default.
• W2085065303 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3796152" @default.
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