Site-specific conjugation for fully controlled glycoconjugate vaccine preparation

Glycoconjugate vaccines are formed by covalently link a carbohydrate antigen to a carrier protein whose role is to achieve a long lasting immune response directed against the carbohydrate antigen. The nature of the sugar antigen, its length, its ratio per carrier protein and the conjugation chemistry impact on both structure and the immune response of a glycoconjugate vaccine. In addition it has long been assumed that the sites at which the carbohydrate antigen is attached can also have an impact. These important issue can now be addressed owing to the development of novel chemoselective ligation reactions as well as techniques such as site-selective mutagenesis, glycoengineering, or extension of the genetic code. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. A synthetic tetrasaccharide representative of the serotype 14 capsular polysaccharide of Streptococcus pneumoniae has been linked using the thiol/maleimide coupling chemistry to four different Pneumococcal surface adhesin A (PsaA) mutants, each harboring a single cysteine mutation at a defined position. Humoral response of these 1 to 1 carbohydrate antigen/PsaA conjugates have been assessed in mice. Our results showed that the carbohydrate antigen-PsaA connectivity impacts the anti-carrier response and raise questions about the design of glycoconjugate vaccine whereby the protein plays the dual role of immunogen and carrier.S

Combining carbohydrate substitutions at bioinspired positions with multivalent presentation towards optimising lectin inhibitors: case study with calixarenes.

Carbohydrate derivatisation and glycocluster formation are both known to enhance avidity for lectin binding. Using a plant toxin and human adhesion/growth-regulatory lectins (inter- and intrafamily comparisons) the effect of their combination is examined. In detail, aromatic substituents were introduced at the 2-N or 30-positions of N-acetyllactosamine and the products conjugated to two types of calix[n]arenes (n=4, 6) via thiourealinker chemistry

Preparation and In Vitro Antibacterial Activity of 9-O-Glycosyloxime Derivatives of Erythromycin A, a New Class of Macrolide Antibiotics.

International audienc

SN 2 Displacement of Carbohydrate Triflates by 9-Oximes of Erythromycin A and Of a Tylosin Derivative

International audienc

Synthesis and Biological Activity of Natural Aminocyclopentitol Glycosidase Inhibitors: Mannostatins, Trehazolin, Allosamidins, and Their Analogues

International audienc

A one dose experimental cholera vaccine

International audienc

Convergent synthesis of fluorescein-labelled lysine-based cluster glycosides

International audienc

Access to Antigens Related to Anthrose Using Pivotal Cyclic Sulfite/Sulfate Intermediates

International audienc

Convergent synthesis of D-(−)-quinic and shikimic acid-containing dendrimers as potential C-lectin ligands by sulfide ligation of unprotected fragments

International audienc

Les galectines

Les galectines forment une famille de lectines animales solubles caractérisées par leur domaine de liaison aux sucres, conservé au cours de l’évolution, et leur affinité pour des glycoconjugués contenant des β-galactosides. Chaque galectine présente un profil d’expression spatio-temporelle, des ligands et des partenaires spécifiques. Ces lectines sont localisées en intra ou extracellulaire et modulent divers processus cellulaires, dont l’adhérence intercellulaire ou avec la matrice extracellulaire, l’organisation de domaines membranaires, la signalisation cellulaire, le trafic intracellulaire, l’apoptose et la régulation du cycle cellulaire. Les souris ayant une mutation nulle pour les galectines 1, 3 ou 7 sont viables, mais présentent des défauts multiples en condition de stress. La participation des galectines à ces multiples processus les désignent comme des cibles thérapeutiques de choix, en particulier dans les cancers et les maladies inflammatoires