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- Title
Small-molecule mimics of an α-helix for efficient transport of proteins into cells.
- Authors
Okuyama, Masahiro; Laman, Heike; Kingsbury, Sarah R; Visintin, Cristina; Leo, Elisabetta; Eward, Kathryn Leigh; Stoeber, Kai; Boshoff, Chris; Williams, Gareth H; Selwood, David L
- Abstract
We designed and synthesized small-molecule mimics of an alpha-helical peptide protein transduction domain (PTD). These small-molecule carriers, which we termed SMoCs, are easily coupled to biomolecules, and efficiently deliver dye molecules and recombinant proteins into a variety of cell types. We designed the SMoCs using molecular modeling techniques. As an example of a protein cargo, we applied this new technology to the internalization of the DNA replication licensing repressor geminin, in vitro, providing evidence that extracellularly delivered SMoC-geminin can have an antiproliferative effect on human cancer cells. Uptake of SMoC-geminin was inhibited at 4 °C and by chlorpromazine, a compound that induces misassembly of clathrin-coated pits at the cell surface. Thus the mechanism of uptake is likely to be clathrin-mediated endocytosis.
- Subjects
PROTEINS; GENETIC transduction; BIOMOLECULES; RECOMBINANT proteins; DNA replication
- Publication
Nature Methods, 2007, Vol 4, Issue 2, p153
- ISSN
1548-7091
- Publication type
Article
- DOI
10.1038/nmeth997