Development of a delivery vehicle for intracellular transport of botulinum neurotoxin antagonists

FEBS Letters
Michael C GoodnoughMichael Adler

Abstract

A targeted delivery vehicle (DV) was developed for intracellular transport of emerging botulinum neurotoxin (BoNT) antagonists. The DV consisted of the isolated heavy chain (HC) of BoNT/A coupled to a 10-kDa amino dextran via the heterobifunctional linker 3-(2-pyridylthio)-propionyl hydrazide. The HC served to target BoNT-sensitive cells and promote internalization of the complex, while the dextran served as a platform to deliver model therapeutic molecules to the targeted cells. To determine the ability of this chimeric glycoprotein to enter neurons, dextran and HC were labeled independently with the fluorescent dyes Oregon green 488 and Cy3, respectively. Internalization of DV was monitored in primary cortical cells using laser confocal microscopy. Incubation of cells for 24 h with DV resulted in discrete punctate labeling of both soma and processes. The Cy3 and Oregon green 488 signals were generally co-localized, suggesting that the complex remained in the same intracellular compartment during the initial 24 h. The DV-associated fluorescence was reduced progressively by co-application of increasing concentrations of unlabeled BoNT/A holotoxin. The results suggest that the BoNT/A HC is able to mediate internalization of a co...Continue Reading

References

Oct 1, 1992·Applied and Environmental Microbiology·M C Goodnough, E A Johnson
Jul 1, 1994·Molecular Microbiology·C Montecucco, G Schiavo
Mar 1, 1997·Toxicon : Official Journal of the International Society on Toxinology·S S DeshpandeM Adler
Apr 1, 1997·Perspectives in Biology and Medicine·E J Schantz, E A Johnson
Aug 6, 1997·JAMA : the Journal of the American Medical Association·D R FranzE M Eitzen
Jul 1, 1997·Toxicon : Official Journal of the International Society on Toxinology·M AdlerR W Wannemacher
Aug 8, 1998·Annals of Internal Medicine·R L ShapiroD L Swerdlow
Jul 1, 1999·Journal of Neurochemistry·C VerderioM Matteoli
Aug 11, 2000·Journal of Neurochemistry·C C MatthewsP S Fishman
Sep 9, 2000·Toxicon : Official Journal of the International Society on Toxinology·M AdlerS S Deshpande
Jan 2, 2001·Biology of the Cell·B P RoquesM C Fournié-Zaluski

❮ Previous
Next ❯

Citations

Aug 6, 2003·Trends in Molecular Medicine·Patrick G ForanFrederic A Meunier
Nov 6, 2010·Protein Engineering, Design & Selection : PEDS·Mengfei HoBrenda A Wilson
Oct 29, 2009·BMC Pharmacology·Peng ZhangPrabhati Ray
Sep 11, 2013·Annual Review of Pharmacology and Toxicology·Geoffrey MasuyerK Ravi Acharya
Apr 21, 2005·Critical Reviews in Microbiology·H D Shukla, S K Sharma
Mar 7, 2009·Toxicon : Official Journal of the International Society on Toxinology·Keith A Foster
Dec 16, 2011·Protein Science : a Publication of the Protein Society·Mengfei HoBrenda A Wilson
Sep 27, 2003·Biochemical and Biophysical Research Communications·James C BurnettSina Bavari
Jan 5, 2010·Protein Expression and Purification·Philip A BandKonstantin Ichtchenko
Mar 30, 2010·Biochimie·Bal Ram SinghPrabhati Ray
Feb 22, 2017·Scientific Reports·Edwin J Vazquez-CintronKonstantin Ichtchenko
Jan 8, 2021·Science Translational Medicine·Patrick M McNuttKonstantin Ichtchenko

❮ Previous
Next ❯

Related Concepts

Related Feeds

Botulism (ASM)

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

Botulism

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.