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Transforming the Domain Structure of Botulinum Neurotoxins into Novel Therapeutics

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Botulinum Neurotoxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 364))

Abstract

Botulinum neurotoxins are comprised of multiple identifiable protein domains. Recent advances in understanding the relationships between domain structure and neurotoxin function have provided a number of opportunities to engineer innovative therapeutic proteins that utilise the neurotoxins and neurotoxin domains. For example, recent insights into the properties of the catalytic, translocation and binding domains open up opportunities to develop botulinum neurotoxins with enhanced properties of selectivity, potency and duration of action. In parallel, the broad scope for utilisation of the individual domains is becoming clearer as significant advancements are made to exploit the unique biology of the catalytic and translocation domains. These opportunities and the status of their development will be reviewed in this chapter.

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Abbreviations

BoNT:

Botulinum neurotoxin

HC:

Heavy chain of BoNT

HC :

C-terminal domain of the Heavy chain of BoNT

HCC :

C-terminal sub-domain of the HC

HN :

N-terminal domain of the heavy chain of BoNT

LC:

Light chain domain of BoNT

LHN :

Fragment of BoNT comprising the LC and HN domains

LHN/C1 :

Fragment of BoNT comprising the LC and HN domains of BoNT/C1

SNAP-25:

Synaptosomal-associated protein of 25 kDa

SNARE:

Soluble N-ethylmaleimide–sensitive factor attachment protein receptor

SV2:

Synaptic vesicle glycoprotein 2

TeNT:

Tetanus neurotoxin

TSI:

Targeted secretion inhibitors

VAMP:

Vesicle associated membrane protein

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Authors and Affiliations

  1. Syntaxin Ltd., Units 4-10, The Quadrant, Abingdon, Oxon, OX14 3YS, UK

    John Chaddock

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  1. John Chaddock
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Correspondence to John Chaddock .

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  1. , Institut für Toxikologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Andreas Rummel

  2. , Institut für Physiologische Chemie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

    Thomas Binz

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Chaddock, J. (2012). Transforming the Domain Structure of Botulinum Neurotoxins into Novel Therapeutics. In: Rummel, A., Binz, T. (eds) Botulinum Neurotoxins. Current Topics in Microbiology and Immunology, vol 364. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33570-9_13

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