Automated Synthesis of C1-Functionalized Oligosaccharides.

Automated glycan assembly (AGA) streamlines the synthesis of complex oligosaccharides. The reducing end of the oligosaccharide serves as an attachment site to the polymer support to liberate a free reducing end or an aminopentanol for ready conjugation to carrier proteins or surfaces. The facile installation of different aglycons on oligosaccharides has not been possible via AGA until now.

Klebsiella pneumoniae Glycoconjugate Vaccine Leads Based on Semi-Synthetic O1 and O2ac Antigens.

Klebsiella pneumoniae (KP) is a common opportunistic pathogen that emerged as a new critical threat to human health, due to its hypervirulence and widespread resistance against many antibiotics, including carbapenems. Alternative intervention strategies such as vaccines are not available. Cell-surface lipopolysaccharides (LPS) and capsular polysaccharides (CPS) are attractive targets for vaccine development.

Semisynthetic Glycoconjugate Vaccine Lead against Serotype O2afg Induces Functional Antibodies and Reduces the Burden of Acute Pneumonia.

Carbapenem-resistant (CR-) bacteria are a serious global health concern due to their drug-resistance to nearly all available antibiotics, fast spread, and high mortality rate. O2afg is a major CR- serotype in the sequence type 258 group (KPST258) that is weakly immunogenic in humans. Here, we describe the creation and evaluation of semisynthetic O2afg glycoconjugate vaccine leads containing one and two repeating units of the polysaccharide epitope that covers the surface of the bacteria conjugated to the carrier protein CRM.

Mechanistic insight into benzylidene-directed glycosylation reactions using cryogenic infrared spectroscopy.

The stereoselective formation of 1,2- glycosidic linkages is challenging. The currently most widely used strategy for their installation uses 4,6--benzylidene-protected building blocks. The stereoselectivity of this reaction is thought to be driven by a covalent intermediate, which reacts via an S2 mechanism.

Convergent synthesis of bicyclic boronates a cascade regioselective Suzuki-Miyaura/cyclisation protocol.

Bicyclic boronates have recently emerged as promising candidates to invoke targeted biomolecular interactions, given their selectivity for specific functionalities. Despite this, the general stability of the C-B bond , for such heterocycles, remains an intractable challenge that can often preclude their utility in drug discovery. To address this challenge, strategies that allow expedient access to strategically substituted boronates, that enable modulation of the C-B bond are urgently required.

Confined Flash Printing and Synthesis of Stable Perovskite Nanofilms under Ambient Conditions.

The fabrication of stable perovskite nanofilm patterns is important for the development of functional optical devices. However, current production approaches are limited by the requirement for strict inert gas protection and long processing times. Here, a confined flash printing synthesis method is presented to generate perovskite nanofilms under ambient conditions, combining precursor transfer, perovskite synthesis, crystallization, and polymer protection in a single step within milliseconds.

Chemical Synthesis and Antigenicity Evaluation of an Aminoglycoside Trisaccharide Repeating Unit of Serotype O5 O-Antigen Containing a Rare Dimeric-ManN3NA.

bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent medical need. While the immunological activity of lipopolysaccharide O-antigens in is well-known, the specific protective epitopes remain unidentified.

Photogeneration of α-Bimetalloid Radicals via Selective Activation of Multifunctional C1 Units.

Light-driven strategies that enable the chemoselective activation of a specific bond in multifunctional systems are comparatively underexplored in comparison to transition-metal-based technologies, yet desirable when considering the controlled exploration of chemical space. With the current drive to discover next-generation therapeutics, reaction design that enables the strategic incorporation of an sp carbon center, containing multiple synthetic handles for the subsequent exploration of chemical space would be highly enabling. Here, we describe the photoactivation of ambiphilic C1 units to generate α-bimetalloid radicals using only a Lewis base and light source to directly activate the C-I bond.

A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C.

Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice.

Dissecting the Conformational Stability of a Glycan Hairpin.

Systematic structural studies of model oligopeptides revealed important aspects of protein folding and offered design principles to access non-natural materials. In the same way, the rules that regulate glycan folding could be established by studying synthetic oligosaccharide models. However, their analysis is often limited due to the synthetic and analytical complexity.

Phosphates as Assisting Groups in Glycan Synthesis.

In nature, phosphates are added to and cleaved from molecules to direct biological pathways. The concept was adapted to overcome limitations in the chemical synthesis of complex oligosaccharides. Phosphates were chemically placed on synthetic glycans to ensure site-specific enzymatic elongation by sialylation.

In situ Tracking of Exoenzyme Activity Using Droplet Luminescence Concentrators for Ratiometric Detection of Bacteria.

We demonstrate a novel, rapid, and cost-effective biosensing paradigm that is based on an in situ visualization of bacterial exoenzyme activity using biphasic Janus emulsion droplets. Sensitization of the droplets toward dominant extracellular enzymes of bacterial pathogens is realized via selective functionalization of one hemisphere of Janus droplets with enzyme-cleavable surfactants. Surfactant cleavage results in an interfacial tension increase at the respective droplet interface, which readily transduces into a microscopically detectable change of the internal droplet morphologies.

Metal-free photoanodes for C-H functionalization.

Organic semiconductors, such as carbon nitride, when employed as powders, show attractive photocatalytic properties, but their photoelectrochemical performance suffers from low charge transport capability, charge carrier recombination, and self-oxidation. High film-substrate affinity and well-designed heterojunction structures may address these issues, achieved through advanced film generation techniques. Here, we introduce a spin coating pretreatment of a conductive substrate with a multipurpose polymer and a supramolecular precursor, followed by chemical vapor deposition for the synthesis of dual-layer carbon nitride photoelectrodes.

Controlling the Assembly of Cellulose-Based Oligosaccharides through Sequence Modifications.

Peptides and nucleic acids with programmable sequences are widely explored for the production of tunable, self-assembling functional materials. Herein we demonstrate that the primary sequence of oligosaccharides can be designed to access materials with tunable shapes and properties. Synthetic cellulose-based oligomers were assembled into 2D or 3D rod-like crystallites.

Visualizing Chiral Interactions in Carbohydrates Adsorbed on Au(111) by High-Resolution STM Imaging.

Carbohydrates are the most abundant organic material on Earth and the structural "material of choice" in many living systems. Nevertheless, design and engineering of synthetic carbohydrate materials presently lag behind that for protein and nucleic acids. Bottom-up engineering of carbohydrate materials demands an atomic-level understanding of their molecular structures and interactions in condensed phases.

Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses.

Influenza A viruses (IAVs) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycans on host cells. HA's receptor specificity towards individual glycans is well studied and clearly critical for virus infection, but the contribution of the highly heterogeneous and complex glycocalyx to virus-cell adhesion remains elusive. Here, we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS), to compare influenza virus receptor specificity with virus binding to live cells.

Synthesis of oligosaccharides to identify an immunologically active epitope against infection.

() is an emerging multidrug-resistant fungal pathogen that represents a significant public health challenge as it can spread rapidly and result in high mortality rates. The mannans on the cell surface are potent immunogens and attractive targets for developing a glycoconjugate vaccine. We synthesized the oligosaccharides resembling cell surface mannans of and printed them onto microarray slides that were used to screen plasma from mice infected with .