Duplication of clostridial binding domains for enhanced macromolecular delivery into neurons.

ABSTRACT: Neurological diseases constitute a quarter of global disease burden and are expected to rise worldwide with the ageing of human populations. There is an increasing need to develop new molecular systems which can deliver drugs specifically into neurons, non-dividing cells meant to last a human lifetime. Neuronal drug delivery must rely on agents which can recognise neurons with high specificity and affinity. Here we used a recently introduced 'stapling' system to prepare macromolecules carrying duplicated binding domains from the clostridial family of neurotoxins. We engineered individual parts of clostridial neurotoxins separately and combined them using a strong alpha-helical bundle. We show that combining two identical binding domains of tetanus and botulinum type D neurotoxins, in a ste

SUBMITTER: Leese C 

PROVIDER: S-EPMC7043326 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature