3 research outputs found
Electronic Detection of Lectins Using Carbohydrate-Functionalized Nanostructures: Graphene <i>versus</i> Carbon Nanotubes
Here we investigated the interactions between lectins and carbohydrates using field-effect transistor (FET) devices comprised of chemically converted graphene (CCG) and single-walled carbon nanotubes (SWNTs). Pyrene- and porphyrin-based glycoconjugates were functionalized noncovalently on the surface of CCG-FET and SWNT-FET devices, which were then treated with 2 μM nonspecific and specific lectins. In particular, three different lectins (PA-IL, PA-IIL, and ConA) and three carbohydrate epitopes (galactose, fucose, and mannose) were tested. The responses of 36 different devices were compared and rationalized using computer-aided models of carbon nanostructure/glycoconjugate interactions. Glycoconjugate surface coverage in addition to one-dimensional structures of SWNTs resulted in optimal lectin detection. Additionally, lectin titration data of SWNT- and CCG-based biosensors were used to calculate lectin dissociation constants (<i>K</i><sub>d</sub>) and compare them to the values obtained from the isothermal titration microcalorimetry technique
Synthesis of a Library of Fucosylated Glycoclusters and Determination of their Binding toward Pseudomonas aeruginosa Lectin B (PA-IIL) Using a DNA-Based Carbohydrate Microarray
Pseudomonas aeruginosa (PA) is a
Gram negative opportunistic pathogen and is the major pathogen encounter
in the cystic fibrosis (CF) lung airways. It often leads to chronic
respiratory infection despite aggressive antibiotic therapy due to
the emergence of resistant strains and to the formation of biofilm.
The lectin PA-IIL (LecB) is a fucose-specific lectin from PA suspected
to be involved in host recognition/adhesion and in biofilm formation.
Thus, it can be foreseen as a potential therapeutic target. Herein,
16 fucosylated glycoclusters with antenna-like, linear, or crown-like
spatial arrangements were synthesized using a combination of DNA solid-phase
synthesis and alkyne azide 1,3-dipolar cycloaddition (CuAAC). Their
binding properties toward PA-IIL were then evaluated based on DNA
directed immobilization (DDI) carbohydrate microarray. Our results
suggested that the antenna-like scaffold was preferred to linear or
crown-like glycoclusters. Among the crown-like carbohydrate centered
fucosylated glycoclusters, mannose-based core was better than glucose-
and galactose-based ones. The influence of the linker arm was also
evaluated, and long linkers between fucoses and the core led to a
slight better binding than the short ones
Antiadhesive Properties of Glycoclusters against <i>Pseudomonas aeruginosa</i> Lung Infection
<i>Pseudomonas aeruginosa</i> lung infections are a major
cause of death in cystic fibrosis and hospitalized patients. Treating
these infections is becoming difficult due to the emergence of conventional
antimicrobial multiresistance. While monosaccharides have proved beneficial
against such bacterial lung infection, the design of several multivalent
glycosylated macromolecules has been shown to be also beneficial on
biofilm dispersion. In this study, calix[4]arene-based glycoclusters
functionalized with galactosides or fucosides have been synthesized.
The characterization of their inhibitory properties on <i>Pseudomonas
aeruginosa</i> aggregation, biofilm formation, adhesion on epithelial
cells, and destruction of alveolar tissues were performed. The antiadhesive
properties of the designed glycoclusters were demonstrated through
several in vitro bioassays. An in vivo mouse model of lung infection
provided an almost complete protection against <i>Pseudomonas
aeruginosa</i> with the designed glycoclusters