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Aggregation-mediated macromolecular uptake by a molecular transporter.

Abstract：

:Endocytosis is a key process in cellular delivery of macromolecules by molecular transporters, although the mechanism of internalization remains unclear. Here, we probe the cellular uptake of streptavidin using biotinylated guanidinoneomycin (biotinGNeo), a low molecular weight guanidinium-rich molecular transporter. Two distinct modes were explored: (i) incubation of cells with a preformed tetravalent streptavidin-(biotinGNeo)4 conjugate and (ii) preincubation of cells with the biotinGNeo before exposure to streptavidin. A significant enhancement in uptake was observed after preincubation with biotinGNeo. FRET studies showed that the enhanced uptake was accompanied by extensive aggregation of streptavidin on the cell surface. Because guanidinylated neomycin was previously found to exclusively bind to heparan sulfate, our observations suggest that heparan sulfate proteoglycan aggregation is a pivotal step for endocytic entry into cells by guanidinoglycosides. These observations put forward a practical and general pathway for the cellular delivery of diverse macromolecules.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Inoue M,Tong W,Esko JD,Tor Y

doi

10.1021/cb400172h

subject

Has Abstract

pub_date

2013-07-19 00:00:00

pages

1383-8

issue

7

eissn

1554-8929

issn

1554-8937

journal_volume

8

pub_type

信件

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