Trehalose-based Janus cyclooligosaccharides: the "Click" synthesis and DNA-directed assembly into pH-sensitive transfectious nanoparticles.

The convergent preparation of Janus molecular nanoparticles by thiourea-"clicking" of α,α'-trehalose halves has been implemented; the strategy allows access to macrocyclic derivatives with seggregated cationic and lipophilic domains that in the presence of DNA undergo pH-dependent self-assembly into lamellar superstructures, as established by electrochemical, structural (SAXS), microscopical (TEM) and computational techniques, that mediate transfection in vitro and in vivo.

Recent developments on synthetic tools towards structural and functional glycodiversity.

Despite being the most abundant type of biopolymers in Nature, the biological relevance of carbohydrates has systematically been underrated for decades, associating them far less sophisticated functions (structural or energy sourcing) than those unraveled for polynucleotides and proteins. The inherently large and complex diversity of carbohydrates and glycoconjugates, together with the lack of efficient technologies to either isolate them from natural sources or produce them synthetically in useful amounts, have burdened the appreciation of their utmost importance in the most fundamental biological processes. For these reasons, carbohydrate-mediated transmission of biological information was largely unexplored. However, over the decades, it became clear that the expression of complex carbohydrates is critical in the development of living systems. Nature uses this diverse repertoire of structures as codes in fundamental biological processes such as cellular differentiation, cellular signaling, fertilization or immune response, among many others. The urgency to elucidate the glycan code in terms of structure-function relationships has fuelled chemical biology approaches uncovering new frontiers in molecular biology, for which the term glycobiology had to be coined in the early 1980s'. Novel strategies for assembling oligosaccharides, glycoproteins, glycolipids and a range of glycoconjugates have flourished ever since providing access to glycomaterials for interrogating and interfering glycan function. This account focuses on the major breakthroughs made on the strategies during the last decades to synthetically reproduce the overwhelming glycodiversity, emphasizing on the dazzling array of concepts and techniques which development was required to cope with the task. In the first place, a succinct overview of the structural and functional diversity of biologically relevant saccharides and glycoconjugates will be given. Then, a selection of the most relevant strategies that composes the complex and diversity-oriented toolbox that modern carbohydrate synthesis consists on will be dissected. Finally, a selection of the most recent applications of this synthetic toolbox to chemical biology will be captured.

Binding affinity properties of dendritic glycosides based on a beta-cyclodextrin core toward guest molecules and concanavalin A.

The inclusion behavior and concanavalin A binding properties of hepta-antennated and newly synthesized tetradeca-antennated C-6-branched mannopyranosyl and glucopyrannosyl cyclomaltoheptaose (beta-cyclodextrin) derivatives have been evaluated by isothermal titration microcalorimetry and enzyme-linked lectin assay (ELLA), respectively. The synthesis of three first-order dendrimers based on a beta-cyclodextrin core containing 14 1-thio-beta-D-glucose, 1-thio-beta-mannose, and 1-thio-beta-rhamnose residues was performed following a convergent approach and involving (1) preparation of a thiolated bis-branched glycoside building block and (2) attachment of the building block onto heptakis(6-deoxy-6-iodo)-beta-cyclodextrin. Calorimetric titrations performed at 25 degrees C in buffered aqueous solution (pH 7.4) gave the affinity constants and the thermodynamic parameters for the inclusion complex formation of these beta-cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalensulfonate (ANS) and 2-naphthalenesulfonate. The host capability of the persubstituted beta-cyclodextrins decreased with respect to the native beta-CD when sodium 2-naphthalenesulfonate was used as a guest and improved when ANS was used as a guest molecule. Heptavalent mannoclusters based on beta-CD cores enhance the lectin binding affinity due to the cluster effect; however, the increase of the valency from 7 to 14 ligands did not contribute to the improvement of the concanavalin A binding affinity. In addition, the synthesized hyperbranched mannoCDs lost completely the capability as a host molecules.