In this study, we demonstrate that appendage of a single asparagusic acid residue (AspA tag) is sufficient to ensure efficient cellular uptake and intracellular distribution of fully unprotected peptides. We apply this new delivery method to induce apoptotic response in cancer cells using long (up to 20mer) BH3 domain peptides. Moreover, to understand the molecular mechanism of the cellular uptake, we perform chemical proteomics experiments and identify the direct molecular targets of the asparagusic acid tag. Our findings document covalent bond formation between the asparagusic acid moiety and the cysteines 556 and 558 on the surface of the transferrin receptor resulting in subsequent endocytic uptake of the payload. We believe that the small size, low cellular toxicity and the efficient transferrin receptor-mediated uptake render the AspA tag highly attractive for various life science applications.
机构:
Harvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Abraham, Jonathan
Corbett, Kevin D.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Corbett, Kevin D.
Farzan, Michael
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, New England Primate Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Farzan, Michael
Choe, Hyeryun
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Choe, Hyeryun
Harrison, Stephen C.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
机构:
Univ Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, FranceUniv Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, France
Bechara, Cherine
Sagan, Sandrine
论文数: 0引用数: 0
h-index: 0
机构:
Univ Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, FranceUniv Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, France
机构:
Harvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Abraham, Jonathan
Corbett, Kevin D.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Corbett, Kevin D.
Farzan, Michael
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, New England Primate Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Farzan, Michael
Choe, Hyeryun
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Choe, Hyeryun
Harrison, Stephen C.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USAHarvard Univ, Sch Med, Mol Med Lab, Boston, MA 02115 USA
机构:
Univ Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, FranceUniv Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, France
Bechara, Cherine
Sagan, Sandrine
论文数: 0引用数: 0
h-index: 0
机构:
Univ Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, FranceUniv Paris 06, Lab BioMol, Cc 182, ENS,UMR CNRS 7203, F-75252 Paris 05, France