Poster Presentation Royal Australian Chemical Institute National Congress 2026

Harnessing Retrograde Axonal Transport Through Simple Protein-Drug Conjugation (#110)

Karen Hakobyan 1 , Joel Yong 2 , Jake Violi 3 , Guangzhao Mao 4 , Jiangtao Xu 2
  1. Adelaide University, Adelaide, SA, Australia
  2. School of Chemical Engineering, University of New South Wales, Sydney, NSW, Australia
  3. School of Chemistry, University of New South Wales, Sydney, NSW, Australia
  4. School of Engineering, University of Edinburgh, Edinburgh, Scotland, United Kingdom

Retrograde axonal transport is a mainstay in the toolkit of histology. Fascinatingly, it is a mass transport mode which exists endogenously in neurons and completely bypasses the blood-CNS barriers. Exogenous substances which can undergo this mode of mass transport include miscellaneous small-molecular dyes, viruses and lectins. Despite this, axonal transport remains completely underutilised as a mode of mass transport in living organisms, for example, as a potential drug delivery mode. As the first key step to realise this, simple conjugation methodologies are required. As such, this presentation will disclose our efforts to address this problem on a practical level. In the putative example, an adenosine receptor antagonist (dipropylcyclopentylxanthine -- DPCPX), an otherwise unreactive compound, was conjugated to a lectin (wheat germ agglutinin -- WGA) using very simple dialdehyde chemistry. Despite the relatively divergent nature of dialdehyde chemistry, we demonstrate through through chemical characterisation and in vitro biology that not only did a conjugation occur, but the kinetics of drug release could be measured, and that the activity of neither component was seriously compromised through the conjugation, while being minimally toxic within relevant concentration range.