Aromatic ynamines : a new bio-orthogonal reactive group for step-efficient, sequential bioconjugation

  • Marine Hatit

Student thesis: Doctoral Thesis

Abstract

The Cu-catalysed alkyne-azide cycloaddition (CuAAC) or 'click' reaction is a powerful and robust bio-orthogonal reaction that exclusively produces 1,4-substituted triazoles. Despite its extensive utility in chemical biology, the ability to differentiate alkyne subtypes has received little attention as a tool for the construction of discrete bioconjugates. This work highlights the utility of aromatic ynamines as a new click reagent for sequential bioconjugation. Aromatic ynamines are superior click reagents with enhanced chemical reactivity relative to conventional alkynes. This unique and orthogonal reactivity profile circumvents the need for conventional protecting group strategies.This project will also highlight the biocompatibility of these reagents as a new tool for protecting-group free sequential CuAAC bioconjugation of oligonucleotides in the presence of more accessible competing alkyne substrate (Scheme 1). This strategy allows the formation of a new platform for specific labelling using fluorescent and PET probes as much as specific targeting and drug delivery. Importantly, higher reactivity of aromatic ynamines allows lower copper loading, thereby decreases toxicity and side reactions on biomolecules.[Graphic with the following title:] Scheme 1. Chemoslective, sequential CuAAC bioconjugation using enhanced reactivity of aromatic ynamines
Date of Award8 Jan 2019
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorGlenn Burley (Supervisor) & Allan Watson (Supervisor)

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