Faculty Opinions recommendation of Oligocarbonate molecular transporters: oligomerization-based syntheses and cell-penetrating studies.
Year: 2011
Type: peer-review
Abstract: A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-sidechain spacing is described.Conjugates can be rapidly assembled irrespective of length in a one step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs).The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme.New strategies, devices and agents that enable or enhance the passage of drugs or probes across biological barriers are required to address a range of major challenges in chemotherapy, imaging, diagnostics, and mechanistic chemical biology. 1 In 2000, we reported that the cellular uptake of the Tat 49-57 peptide could be mimicked by homooligomers of arginine.2 Uptake was shown to be a function of the number and array of guanidinium groups, observations that led to the design and synthesis of the first guanidinium-rich (GR) peptoids, 2 GR-spaced peptides, 3 GR-oligocarbamates 4 and GR-dendrimeric molecular transporters (MoTrs).5 Noteworthy subsequent studies from several groups showed that a variety of other scaffolds, including betapeptides, carbohydrates, heterocycles, and peptide nucleic acids, upon perguanidinylation, exhibit cell-penetrating activity.6 GR MoTrs have been shown to carry a variety of cargos into cells, including small molecules, probes, metals, peptides, proteins, siRNA, morpholino-RNAs, and DNA plasmids.7 Activatable MoTrs have been reported for targeted therapy and imaging, 8 a releasable octaarginine-drug conjugate has been shown to overcome Pgp-mediated resistance in animal models of cancer, 9 and a drug-heptaarginine conjugate has been advanced to phase II human clinical trials.
Author: Gregory Tew
Institution: University of Massachusetts Amherst
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4206379545