Synthesis and functionalization of nanoplatforms targeting bacterial adhesion and multivalent enzyme inhibition.

  • Marta Abellán Flos

Student thesis: Doc typesDoctor of Sciences


Because of its critical role in major biological phenomena, multivalency has received much attention in biomedicine in the last few years. Many natural processes take advantage of the multimeric presentation of biological entities to enhance the efficiency of binding events. This is particularly true for carbohydrate-protein interactions, which are notoriously weak at the monomer level, but can be dramatically strengthened if the ligand is presented in a multivalent manner (glycoside cluster effect). Inspired by these natural phenomena, scientists have dedicated tremendous effort both to understand the underlying mechanisms of multivalency and to create artificial multivalent systems for diverse applications, such as the inhibition of the adhesion of pathogenic bacteria to their host tissues (mediated by multivalent binding lectin-carbohydrate, in bacteria and cell glycocalyx respectively) to prevent infections. Indeed, lectin-carbohydrate multivalent interactions, probably the most studied ones, take place as the first step of some viral and bacterial infections. Lectins are carbohydrate-binding proteins that often display more than one binding site and are widely overexpressed on the biological surface, thus favoring the interaction with multimeric presentation of their carbohydrate ligands. One of the most studied bacterial lectins is FimH, a mannose-specific adhesin involved in the infection of uropathogenic E. coli. In the first part of this thesis, we investigated by several techniques how different glycoclusters, i.e. architectures displaying multiple copies of carbohydrates, may inhibit the adhesion of E. coli mediated by FimH.
The second part of the thesis deals with the multivalent inhibition of enzymes. Traditionally, the inhibition of enzymes has been attempted by designing transition state mimics with increased affinity for the binding site due to the fact that, generally, enzymes are monomeric and/or display only one catalytic site, usually of difficult access. However, in 2009, a clear multivalent effect was demonstrated and quantified in α-mannosidase inhibition by iminosugar clusters. From then, this field has grown exponentially and the multivalent inhibition of many enzymes, mainly glycosidases, has been attempted. Nevertheless, plenty of key questions remain to be addressed and clarified, such as the inhibition mechanisms and the type of enzymes that could possibly be inhibited in a multivalent manner. Herein, we intended to answer some of these questions by the design of novel potent multivalent enzyme inhibitors against relevant glycosidases and carbonic anhydrases.
Date of Award9 Dec 2015
Original languageEnglish
Awarding Institution
  • University of Namur
SupervisorStephane VINCENT (Supervisor), Daniel Vercauteren (President), Davide BONIFAZI (Jury), W. Bruce Turnbull (Jury) & C. Marta Galan (Jury)


  • Fullerene sugar balls
  • fullerene
  • glycofullerene
  • anti-adhesion
  • anti-virulence
  • mulitvalency
  • carbonic anhydrase
  • multivalent enzyme inhibitor
  • diabetes
  • glycosidase
  • borromeate

Cite this

Synthesis and functionalization of nanoplatforms targeting bacterial adhesion and multivalent enzyme inhibition.
Abellán Flos, M. (Author). 9 Dec 2015

Student thesis: Doc typesDoctor of Sciences