Synthesis of Mannosylated Glycodendrimers and Evaluation against BC2L‐A Lectin from Burkholderia Cenocepacia

Abstract

Chronic colonization of lungs by opportunist bacteria is the major cause of mortality for cystic fibrosis patients. Among these pathogens, Burkholderia cenocepacia is responsible for cepacia syndrome, a deadly exacerbation of infection that is the main cause of poor outcomes of lung transplantation. This bacterium contains three soluble carbohydrate‐binding proteins, including the B. cenocepacia lectin A (BC2L‐A), which is proposed to bind to oligomannose‐type N‐glycan structures to adhere to host tissues. In this work, several mannosylated glycoclusters and glycodendrimers with valencies ranging from four to 24 were prepared and their interactions with BC2L‐A were thermodynamically characterized by isothermal titration calorimetry. The results show that a 24‐valent structure binds to BC2L‐A at nanomolar concentration, which makes this compound the highest affinity monodisperse ligand for this lectin.

Multifunctional Glycoconjugates for Recruiting Natural Antibodies against Cancer Cells

“…Therefore, we decided to synthesized tetra‐ and hexadecavalent Rha‐based ABMs (Scheme ) by using peptide carriers previously identified as well‐suited scaffolds for multivalent presentation of sugars . Starting from the tetraazido cyclodecapeptide 1 , a first CuAAC reaction with propargyl l ‐rhamnopyranoside afforded the tetravalent cluster 2 . On one hand, the introduction of azidoacetic acid on the remaining free lysine residue led to the tetravalent ABM 3 .…”

“…Therefore, we decided to synthesized tetra-and hexadecavalent Rha-basedA BMs (Scheme 1) by using peptidec arriers previouslyi dentified as well-suited scaffolds form ultivalent presentation of sugars. [18,19] Startingf rom the tetraazidoc yclodecapeptide 1, [20] af irst CuAAC reactionw ith propargyl l-rhamnopyranoside [21] afforded the tetravalent cluster 2.O no ne hand, the introduction of azidoacetic acid on the remaining free lysine residue led to the tetravalent ABM 3.O nt he other hand, functionalization of this lysine with pentynoic acid allowed for as econd CuAAC reaction. Intermediate 4 was reacted with 1,y ieldingd endrimer 5.…”

Identification of Nanomolar Lectin Ligands by a Glycodendrimer Microarray

“…First, tetravalent glycoclusters 2 and 4 were prepared by CuAAC conjugation of propargyl 2-deoxy-2-acetamido-α- d -galactopyranoside 32 on azido-functionalized cyclodecapeptide 1 and polylysine dendron 3 ( Scheme 1 ). 30 Monofunctionalized compound 5 was also prepared, as a monomeric reference, and clusters 6 and 7 displaying hydroxymethyl and α-mannoside residues, respectively, were chosen to serve as negative controls in the binding studies.…”

Cyclopeptide scaffolds in carbohydrate-based synthetic vaccines

“…For example, it was recently proven suitable in diverse research fields, in particular for the synthesis of multivalent glycosylated structures with nanomolar affinity towards lectins. [37][38][39][40][41] For all these reasons, cyclopeptides represent interesting carriers to conjugate carbohydrate and peptide epitopes for the preparation of fully synthetic carbohydrate vaccines.…”