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An engineered hCRBPII protein binds a coumarin-based fluorophore to yield a photoswitchable system via Michael/retro-Michael addition of a cysteine residue. Alternate UV/visible light irradiation accesses the two optical states.

Vaccines are critical tools to treat and prevent diseases. For an effective conjugate vaccine, the carrier is crucial, but few carriers are available for clinical applications. In addition, a drawback of current protein carriers is that high levels of antibodies against the carrier are induced by the conjugate vaccine, which are known to interfere with the immune responses against the target antigen. To overcome these challenges, we obtained the near atomic resolution crystal structure of an emerging protein carrier, i.e., the bacteriophage Qβ virus like particle. On the basis of the detailed structural information, novel mutants of bacteriophage Qβ (mQβ) have been designed, which upon conjugation with tumor associated carbohydrate antigens (TACAs), a class of important tumor antigens, elicited powerful anti-TACA IgG responses and yet produced lower levels of anticarrier antibodies as compared to those from the wild type Qβ-TACA conjugates. In a therapeutic model against an aggressive breast cancer in mice, 100% unimmunized mice succumbed to tumors in just 12 days even with chemotherapy. In contrast, 80% of mice immunized with the mQβ-TACA conjugate were completely free from tumors. Besides TACAs, to aid in the development of vaccines to protect against COVID-19, the mQβ based conjugate vaccine has been shown to induce high levels of IgG antibodies against peptide antigens from the SARS-CoV-2 virus, demonstrating its generality. Thus, mQβ is a promising next-generation carrier platform for conjugate vaccines, and structure-based rational design is a powerful strategy to develop new vaccine carriers.

With the emergence of multidrug resistant Salmonella strains, the development of anti-Salmonella vaccines is an important task. Currently there are no approved vaccines against Salmonella Paratyphi A, the leading cause of paratyphoid fever. To fill this gap, oligosaccharides corresponding to the O-polysaccharide repeating units from the surface of Salmonella Paratyphi A have been synthesized through convergent stereoselective glycosylations. The synthetic glycan antigen was conjugated with a powerful immunogenic carrier system, the bacteriophage Qβ. The resulting construct was able to elicit strong and long-lasting anti-glycan IgG antibody responses, which were highly selective toward Salmonella Paratyphi A associated glycans. The availability of well-defined glycan antigen enabled the determination that one repeating unit of the polysaccharide is sufficient to induce protective antibodies, and the paratose residue and/or the O-acetyl modifications on the backbone are important for recognition by antibodies elicited by a Qβ-tetrasaccharide conjugate. Immune sera provided excellent protection to mice from lethal challenge with Salmonella Paratyphi A, highlighting the potential of the synthetic glycan-based vaccine.

The 60-year high Bordetella pertussis (B. pertussis) infection rate in the world suggests the urgent need for new anti-pertussis vaccines. Lipopolysaccharide (LPS) of B. pertussis is an attractive antigen for vaccine development. With the presence of multiple rare sugars and unusual glycosyl linkages, B. pertussis LPS is a highly challenging synthetic target. In this work, aided by molecular dynamics simulation and modeling, the pertussis LPS like pentasaccharide was chemically synthesized for the first time. The pentasaccharide was conjugated with a powerful carrier, bacteriophage Qβ as a vaccine candidate. Immunization of mice with the conjugate induced robust anti-glycan IgG responses with IgG titers reaching several million enzyme-linked immunosorbent assay (ELISA) units. The antibodies generated were long lasting and boostable, and could recognize multiple clinical strains of B. pertussis, highlighting the potential of Qβ-glycan as a new anti-pertussis vaccine.

Proteoglycans have important biological activities. To improve the overall synthetic efficiency, a new chemoenzymatic route has been established for the proteoglycan linkage region bearing a galactose-xylose disaccharide. The xylosylated glycopeptides were synthesized via solid phase synthesis, which was followed by the addition of the galactose unit by the galactosyl transferase β4GalT7. This work leads to a better understanding of the acceptor preference of β4GalT7 and opens the door for expeditious synthesis of the proteoglycan linkage region.

FR-1V, a fluorene-based aldehydic chromophore, binds its target protein as an imine to yield a highly bathochromic pigment, CF-2, a prototypic protein-dye tagging system whose NIR emission can be spatiotemporally switched ON by rapid UV-light activation. This is achieved through photoisomerization of the imine and its subsequent protonation. We demonstrate a no-wash protocol for live cell imaging of subcellular compartments in a variety of mammalian cell lines with minimal fluorescence background.

Mutants of human cellular retinol-binding protein II (hCRBPII) were engineered to bind a julolidine retinal analogue for the purpose of developing a ratiometric pH sensor. The design relied on the electrostatic influence of a titratable amino acid side chain, which affects the absorption and, thus, the emission of the protein/fluorophore complex. The ratio of emissions obtained at two excitation wavelengths that correspond to the absorption of the two forms of the protein/fluorophore complex, leads to a concentration-independent measure of pH.

The first synthetic carbohydrate based potential anti-Salmonella Enteritidis vaccine has been developed by conjugating a synthetic tetrasaccharide antigen with bacteriophage Qβ. High levels of specific and long lasting anti-glycan IgG antibodies were induced by the conjugate, which completely protected mice from lethal bacterial challenges in a passive transfer model.

Engineered nanoparticles (ENPs) are known to possess unique size and shape dependent chemical and physical properties. As a result of their properties, ENPs have been effective in several important applications including catalysis, sensor design, photonics, electronics, medicine, and the environmental remediation of toxic pollutants. Such properties and applications have led to an increase in the manufacture of ENPs and a rise in their presence in consumer products. The increase of ENPs in consumer products presents several opportunities and challenges, and necessitates a proactive study of their health and safety. This article highlights some recent work in which we have studied the effect of exposure of well-defined ENPs to pesticides and the effect of pH and dissolved organic matter. We also summarize our work and that of others who have studied the toxicity of ENPs with microorganisms. The results provide insights on the need for green manufacturing strategies of ENPs, their use and safe disposal practices.

The unique chemical and physical properties of nanoscale materials have led to important roles in several scientific and technological fields. Environmental chemistry processes have benefited from the enhanced reactivity of nanoscale particles relative to their bulk counterparts with contaminants. Here, we describe recent advances in the synthesis and characterization of metallic and bimetallic nanoparticles that have been effective toward degrading toxic organohalide contaminants. We then review the degradation mechanisms involved in the reactions of nanoscale particles with organohalides via reduction pathways. We also discuss an emerging area – the degradation of organohalides via multi-electron transfer pathways.

The development of materials that are efficient in biomass conversion is one of the fastest growing areas of science and technology research. Heterogeneous catalysis and enzymatic-based processes have played a vital role in these processes. In recent years, nanoscale materials have emerged as pivotal components toward the catalysis of significant chemical and biochemical reactions. This chapter summarizes some of the key roles that metallic and bimetallic nanomaterials have played in biomass conversion. Significant emphasis has been devoted to describing advances in oxidation of small molecules, cellulose conversion, fatty acid decarboxylation, production of liquid fuels and the design of fuel cells. The sustainable preparation of these nanomaterials is also described.

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