@article{prasanna_semisynthetic_2023,

title = {Semisynthetic Pneumococcal Glycoconjugate Nanovaccine},

author = {Maruthi Prasanna and Rubén Varela Calvino and Annie Lambert and Maria Arista Romero and Sylvia Pujals and François Trottein and Emilie Camberlein and Cyrille Grandjean and Noemi Csaba},

url = {https://doi.org/10.1021/acs.bioconjchem.3c00252},

doi = {10.1021/acs.bioconjchem.3c00252},

issn = {1043-1802},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {Bioconjugate Chemistry},

volume = {34},

number = {9},

pages = {1563--1575},

abstract = {Pneumococcal conjugate vaccines offer an excellent safety profile and high protection against the serotypes comprised in the vaccine. However, inclusion of protein antigens fromStreptococcus pneumoniaecombined with potent adjuvants and a suitable delivery system are expected to both extend protection to serotype strains not represented in the formulation and stimulate a broader immune response, thus more effective in young children, elderly, and immunocompromised populations. Along this line, nanoparticle (NP) delivery systems can enhance the immunogenicity of antigens by protecting them from degradation and increasing their uptake by antigen-presenting cells, as well as offering co-delivery with adjuvants. We report herein the encapsulation of a semisynthetic glycoconjugate (GC) composed of a synthetic tetrasaccharide mimicking theS. pneumoniae serotype 14 capsular polysaccharide (CP14) linked to the Pneumococcal surface protein A (PsaA) using chitosan NPs (CNPs). These GC-loaded chitosan nanoparticles (GC-CNPs) were not toxic to human monocyte-derived dendritic cells (MoDCs), showed enhanced uptake, and displayed better immunostimulatory properties in comparison to the naked GC. A comparative study was carried out in mice to evaluate the immune response elicited by the glycoconjugate-administered subcutaneously (SC), where the GC-CNPs displayed 100-fold higher IgG response as compared with the group treated with nonencapsulated GC. Overall, the study demonstrates the potential of this chitosan-based nanovaccine for efficient delivery of glycoconjugate antigens.},

note = {Publisher: American Chemical Society},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{violo2023site,

title = {Site-Selective Unnatural Amino Acid Incorporation at Single or Multiple Positions to Control Sugar-Protein Connectivity in Glycoconjugate Vaccine Candidates},

author = {Typhaine Violo and Annie Lambert and Aline Pillot and Mathieu Fanuel and Jessica Mac-Béar and Cédric Broussard and Cyrille Grandjean and Emilie Camberlein},

url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.202203497},

doi = {10.1002/chem.202203497},

isbn = {1521-3765},

year  = {2023},

date = {2023-03-13},

urldate = {2023-01-01},

journal = {Chemistry--A European Journal},

volume = {29},

number = {15},

pages = {e202203497},

publisher = {Wiley Online Library},

abstract = {In cellulo site-specific unnatural amino acid incorporation based on amber stop codon reassignment is a powerful tool to modify proteins at defined positions. This technique is herein applied to the selective functionalization of the Pneumococcal surface adhesin A protein at three distinct positions. Nϵ-propargyloxycarbonyl-l-lysine residues were incorporated and their alkyne groups reacted using click-chemistry with a synthetic azido-functionalized tetrasaccharide representative of one repeat unit of the Streptococcus pneumoniae serotype 14 capsular polysaccharide. Anti-PsaA antibody response induced in mice by the trivalent glycoconjugate was determined in comparison with corresponding monovalent and randomly functionalized conjugates. Our results suggest that controlled was superior to random conjugation for preserving antigenicity. In definitive, the reported strategy offers a unique opportunity to study the impact of carbohydrate antigen-carrier protein connectivity on immunogenicity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{prasanna_use_2021,

title = {On the use of adenovirus dodecahedron as a carrier for glycoconjugate vaccines},

author = {Maruthi Prasanna and Malgorzata Podsiadla-Bialoskorska and Damian Mielecki and Nicolas Ruffier and Amina Fateh and Annie Lambert and Mathieu Fanuel and Emilie Camberlein and Ewa Szolajska and Cyrille Grandjean},

url = {https://doi.org/10.1007/s10719-021-09999-3},

doi = {10.1007/s10719-021-09999-3},

issn = {1573-4986},

year  = {2021},

date = {2021-01-01},

urldate = {2021-06-16},

journal = {Glycoconjugate Journal},

abstract = {Virus-Like Particles (VLPs) have been used as immunogenic molecules in numerous recombinant vaccines. VLPs can also serve as vaccine platform to exogenous antigens, usually peptides incorporated within the protein sequences which compose the VLPs or conjugated to them. We herein described the conjugation of a synthetic tetrasaccharide mimicking the Streptococcus pneumoniae serotype 14 capsular polysaccharide to recombinant adenoviral type 3 dodecahedron, formed by the self-assembling of twelve penton bases and investigated the induced immune response when administered subcutaneously (s.c.). Whether formulated in the form of a dodecahedron or disassembled, the glycoconjugate induced an anti-protein response after two and three immunizations equivalent to that observed when the native dodecahedron was administered. On the other hand, the glycoconjugate induced a weak anti-IgM response which diminishes after two doses but no IgM-to-IgG switch was observed in mice against the serotype 14 capsular polysaccharide. In definitive, the whole conjugation process preserved both particulate nature and immunogenicity of the adenoviral dodecahedron. Further studies are needed to fully exploit adenoviral dodecahedron potential in terms of plasticity towards sequence engineering and of its capacity to stimulate the immune system via the intranasal route of administration as well as to shift the response to the carbohydrate antigen by playing both with the carbohydrate to protein ratio and the length of the synthetic carbohydrate antigen.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dussouy2020,

title = {Linear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development.},

author = {Christophe Dussouy and Chandan Kishor and Annie Lambert and Clément Lamoureux and Helen Blanchard and Cyrille Grandjean},

doi = {10.1111/cbdd.13683},

issn = {1747-0285 (Electronic)},

year  = {2020},

date = {2020-03-01},

journal = {Chemical biology & drug design},

abstract = {Galectins play key roles in numerous biological processes. Their mode of action depends on their localization which can be extracellular, cytoplasmic or nuclear, and is partly mediated through interactions with β-galactose containing glycans. Galectins have emerged as novel therapeutic targets notably for the treatment of inflammatory disorders and cancers. This has stimulated the design of carbohydrate-based inhibitors targeting the carbohydrate recognition domains (CRDs) of the galectins. Pursuing this approach, we reasoned that linear oligo-galactosides obtained by straightforward iterative click-chemistry could mimic poly-lactosamine motifs expressed at eukaryote cell surfaces which the extracellular form of galectin-3, a prominent member of the galectin family, specifically recognizes. Affinities towards galectin-3 consistently increased with the length of the representative oligogalactosides but without reaching that of oligo-lactosamines. Elucidation of the X-ray crystal structures of the galectin-3 CRD in complex with a synthesized di- and tri-galactoside confirmed that the compounds bind within the carbohydrate-binding site. The atomic structures revealed that binding interactions mainly occur with the galactose moiety at the non-reducing end, primarily with subsites C and D of the CRD, differing from oligo-lactosamine which bind more consistently across the whole groove formed by the five subsites (A-E) of the galectin-3 CRD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1021/acs.joc.0c01927b,

title = {Access to Galectin-3 Inhibitors from Chemoenzymatic Synthons},

author = {Christophe Dussouy and Stéphane Téletchéa and Annie Lambert and Cathy Charlier and Iuliana Botez and Frédéric De Ceuninck and Cyrille Grandjean},

url = {https://doi.org/10.1021/acs.joc.0c01927},

doi = {10.1021/acs.joc.0c01927},

year  = {2020},

date = {2020-01-01},

journal = {The Journal of Organic Chemistry},

volume = {85},

number = {24},

pages = {16099-16114},

abstract = {Chemoenzymatic strategies are useful for providing both regio- and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus α-glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-d-glucose/glucosamine to lead to β-d-galactopyranosyl-(1→3)-d-glucopyranoside or β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-glucopyranoside derivatives bearing a unique azide function. Taking advantage of the orthogonality between the azide and the hydroxyl functional groups, the former was next selectively reacted to give rise to a library of galectin-3 inhibitors. Combining enzyme substrate promiscuity and bioorthogonality thus appears as a powerful strategy to rapidly access to sugar-based ligands},

note = {PMID: 33200927},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bogoeva2019,

title = {Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3},

author = {Vanya Bogoeva and Miroslav Rangelov and Nadezhda Todorova and Annie Lambert and Clarisse Bridot and Anna Yordanova and Goedele Roos and Cyrille Grandjean and Julie Bouckaert},

doi = {10.3390/molecules24244561},

issn = {14203049},

year  = {2019},

date = {2019-12-01},

journal = {Molecules},

volume = {24},

number = {24},

publisher = {MDPI AG},

abstract = {Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian lectins have been shown to bind oligosaccharide sequences of the aberrant glycosylation pattern found on cancerous tumors. For example human galectin-3, of the galectin family specific for ß-galactoside, is overexpressed in the extracellular matrix of tumorigenous and metastatic tissues. We searched for non-carbohydrate ligands for galectin-3 that can guide a cytotoxic drug to the cancer cells by maintaining its affinity for tumor associated carbohydrate antigens. Previous findings showed that zinc tetrasulfonatophenylporphyrin can bind galectin-3 with sub-micromolar affinity without disturbing lactose binding. Gold(III) porphyrin is not only cytotoxic to cancer cells, it knows also a potential application as photosensitiser in photodynamic therapy. We investigated the binding of gold(III) porphyrin to galectin-3 using different biophysical interaction techniques and demonstrated a low micromolar affinity of human galectin-3 for the cytotoxic compound. Co-crystallization attempts in order to understand the binding mode of gold porphyrin to galectin-3 failed, but molecular docking emphasized a highly populated secondary binding site that does not hinder lactose or Thomsen Friendenreich disaccharide binding. This suggests that gold(III) porphyrin might significantly enhance its concentration and delivery to cancer cells by binding to human galectin-3 that keeps its orientation towards tumor associated carbohydrate antigens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brinkø2019,

title = {Combining Click Reactions for the One-Pot Synthesis of Modular Biomolecule Mimetics},

author = {Anne Brinkø and Christian Risinger and Annie Lambert and Ola Blixt and Cyrille Grandjean and Henrik H Jensen},

doi = {10.1021/acs.orglett.9b02811},

issn = {15237052},

year  = {2019},

date = {2019-01-01},

journal = {Organic Letters},

volume = {21},

number = {18},

pages = {7544--7548},

abstract = {Here, we report on the first combined one-pot use of the two so-called "click reactions": The thiol-ene coupling and the copper-catalyzed alkyne-azide cycloaddition. These reactions were employed in an alternating and one-pot fashion to combine appropriately functionalized monomeric carbohydrate building blocks to create mimics of trisaccharides and tetrasaccharides as single anomers, with only minimal purification necessary. The deprotected oligosaccharide mimics were found to bind both plant lectins and human galectin-3.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pillot2019,

title = {Site-Specific Conjugation for Fully Controlled Glycoconjugate Vaccine Preparation},

author = {Aline Pillot and Alain Defontaine and Amina Fateh and Annie Lambert and Maruthi Prasanna and Mathieu Fanuel and Muriel Pipelier and Noemi Csaba and Typhaine Violo and Emilie Camberlein and Cyrille Grandjean},

doi = {10.3389/fchem.2019.00726},

issn = {22962646},

year  = {2019},

date = {2019-01-01},

journal = {Frontiers in Chemistry},

volume = {7},

number = {November},

pages = {1--9},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{PRASANNA201931,

title = {Semisynthetic glycoconjugate based on dual role protein/PsaA as a pneumococcal vaccine},

author = {Maruthi Prasanna and Daphnée Soulard and Emilie Camberlein and Nicolas Ruffier and Annie Lambert and François Trottein and Noemi Csaba and Cyrille Grandjean},

url = {http://www.sciencedirect.com/science/article/pii/S0928098718305487},

doi = {https://doi.org/10.1016/j.ejps.2018.12.013},

issn = {0928-0987},

year  = {2019},

date = {2019-01-01},

journal = {European Journal of Pharmaceutical Sciences},

volume = {129},

pages = {31--41},

abstract = {Pneumococcal infections remain a major public health concern worldwide. The currently available vaccines in the market are based on pneumococcal capsular polysaccharides but they still need to be improved to secure an optimal coverage notably in population at risk. To circumvent this, association of virulence pneumococcal proteins to the polysaccharide valencies has been proposed with the hope to observe an additive - if not synergistic - protective effect. Along this line, the use of the highly conserved and ubiquitous pneumococcal surface adhesin A (PsaA) as a protein carrier for a synthetic pneumococcal oligosaccharide is demonstrated herein for the first time. A tetrasaccharide mimicking functional antigenic determinants from the S. pneumoniae serotype 14 capsular polysaccharide (Pn14TS) was chemically synthesised. The mature PsaA (mPsaA) was expressed in E. coli and purified using affinity chromatography. The Pn14PS was conjugated to mPsaA using maleimide-thiol coupling chemistry to obtain mPsaA-Pn14PS conjugate (protein/sugar molar ratio: 1/5.4). The mPsaA retained the structural conformation after the conjugation and lyophilisation. The prepared glycoconjugate adjuvanted with α-galactosylceramide, a potent activator of invariant Natural Killer T cells, was tested in mice for its immunological response upon subcutaneous injection in comparison with mPsaA alone and a model BSA conjugate (BSA-Pn14PS, used here as a control). Mice immunised with the mPsaA-Pn14TS produced a robust IgG response against mPsaA and against the capsular polysaccharide from pneumococcal serotype 14. These data provide the basis for novel pneumococcal vaccine development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dion2017c,

title = {Lactosamine-Based Derivatives as Tools to Delineate the Biological Functions of Galectins: Application to Skin Tissue Repair},

author = {Johann Dion and Frédérique Deshayes and Nataliya Storozhylova and Tamara Advedissian and Annie Lambert and Mireille Viguier and Charles Tellier and Christophe Dussouy and Françoise Poirier and Cyrille Grandjean},

doi = {10.1002/cbic.201600673},

issn = {14397633},

year  = {2017},

date = {2017-01-01},

journal = {ChemBioChem},

volume = {18},

number = {8},

pages = {782--789},

abstract = {Galectins have been recognized as potential novel therapeutic targets for the numerous fundamental biological processes in which they are involved. Galectins are key players in homeostasis, and as such their expression and function are finely tuned in vivo. Thus, their modes of action are complex and remain largely unexplored, partly because of the lack of dedicated tools. We thus designed galectin inhibitors from a lactosamine core, functionalized at key C2 and C3′ positions by aromatic substituents to ensure both high affinity and selectivity, and equipped with a spacer that can be modified on demand to further modulate their physico-chemical properties. As a proof-of-concept, galectin-3 was selectively targeted. The efficacy of the synthesized di-aromatic lactosamine tools was shown in cellular assays to modulate collective epithelial cell migration and to interfere with actin/cortactin localization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dion2017a,

title = {Development of a Sensitive Microarray Platform for the Ranking of Galectin Inhibitors: Identification of a Selective Galectin-3 Inhibitor},

author = {Johann Dion and Tamara Advedissian and Nataliya Storozhylova and Samir Dahbi and Annie Lambert and Frédérique Deshayes and Mireille Viguier and Charles Tellier and Françoise Poirier and Stéphane Téletchéa and Christophe Dussouy and Hiroaki Tateno and Jun Hirabayashi and Cyrille Grandjean},

doi = {10.1002/cbic.201700544},

issn = {14397633},

year  = {2017},

date = {2017-01-01},

journal = {ChemBioChem},

volume = {18},

number = {24},

pages = {2428--2440},

abstract = {Glycan microarrays are useful tools for lectin glycan profiling. The use of a glycan microarray based on evanescent-field fluorescence detection was herein further extended to the screening of lectin inhibitors in competitive experiments. The efficacy of this approach was tested with 2/3′-mono- and 2,3′-diaromatic type II lactosamine derivatives and galectins as targets and was validated by comparison with fluorescence anisotropy proposed as an orthogonal protein interaction measurement technique. We showed that subtle differences in the architecture of the inhibitor could be sensed that pointed out the preference of galectin-3 for 2′-arylamido derivatives over ureas, thioureas, and amines and that of galectin-7 for derivatives bearing an α substituent at the anomeric position of glucosamine. We eventually identified a diaromatic oxazoline as a highly specific inhibitor of galectin-3 versus galectin-1 and galectin-7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}