Comparison of Cyclic and Linear PEG Conjugates.

Bioconjugation of polymers to proteins is a method to impart improved stability and pharmacokinetic properties to biologic systems. However, the precise effects of polymer architecture on the resulting bioconjugates are not well understood. Particularly, cyclic polymers are known to possess unique features such as a decreased hydrodynamic radius when compared to their linear counterparts of the same molecular weight, but have not yet been studied. Here, we report the first bioconjugation of a cyclic polymer, poly(ethylene glycol) (PEG), to a model protein, T4 lysozyme, containing a single engineered cysteine residue (V131C). We compare the stability and activity of this conjugate with those of a linear PEG-T4 lysozyme analogue of similar molecular weight. Furthermore, we used molecular dynamics (MD) simulations to determine the behavior of the polymer-protein conjugates in solution. We introduce cyclic polymer-protein conjugates as potential candidates for the improvement of biologic therapeutics.

Ultrafast Au(III)-Mediated Arylation of Cysteine.

Through mechanistic work and rational design, we have developed the fastest organometallic abiotic Cys bioconjugation. As a result, the developed organometallic Au(III) bioconjugation reagents enable selective labeling of Cys moieties down to picomolar concentrations and allow for the rapid construction of complex heterostructures from peptides, proteins, and oligonucleotides. This work showcases how organometallic chemistry can be interfaced with biomolecules and lead to a range of reactivities that are largely unmatched by classical organic chemistry tools.

Efficient end-group functionalization and diblock copolymer synthesis via Au(III) polymer reagents.

Herein, we describe the synthesis of bench-stable organometallic Au(III) terminated polymer reagents. These reagents mediate the chemoselective S-arylation of thiol-containing small molecules and polymers to yield functionalized mono-telechelic polymers and diblock copolymers, respectively. These transformations proceed rapidly within minutes and produce conjugates in quantitative conversion, making this strategy a robust addition to the polymer functionalization toolbox.

Pesticides in honey bee colonies: Establishing a baseline for real world exposure over seven years in the USA.

Honey bees Apis mellifera forage in a wide radius around their colony, bringing back contaminated food resources that can function as terrestrial bioindicators of environmental pesticide exposure. Evaluating pesticide exposure risk to pollinators is an ongoing problem. Here we apply five metrics for pesticide exposure risk (prevalence, diversity, concentration, significant pesticide prevalence, and hazard quotient (HQ)) to a nation-wide field study of honey bees, Apis mellifera in the United States. We examined samples from 1055 apiaries over seven years for 218 different pesticide residues and metabolites, determining that bees were exposed to 120 different pesticide products with a mean of 2.78 per sample. Pesticides in pollen were highly prevalent and variable across states. While pesticide diversity increased over time, most detections occurred at levels predicted to be of low risk to colonies. Varroacides contributed most to concentration, followed by fungicides, while insecticides contributed most to diversity above a toxicity threshold. High risk samples contained one of 12 different insecticides or varroacides. Exposures predicted to be low-risk were nevertheless associated with colony morbidity, and low-level fungicide exposures were tied to queen loss, Nosema infection, and brood diseases.

Implicating ABC Transporters in Insecticide Resistance: Research Strategies and a Decision Framework.

Pest insects damage crops, transmit diseases, and are household nuisances. Historically, they have been controlled with insecticides, but overuse often leads to resistance to one or more of these chemicals. Insects gain resistance to insecticides through behavioral, metabolic, genetic, and physical mechanisms. One frequently overlooked strategy is through the use of ATP-binding cassette (ABC) transporters. ABC transporters, present in all domains of life, perform natural excretory functions, thus the exploitation of these transporters to excrete insecticides and contribute to resistance is highly plausible. Previous work has implicated ABC transporters in some cases of insecticide resistance. Proposed herein is a framework meant as a formal guide for more easily incorporating the analysis of ABC transporters into existing resistance monitoring using suggested simple research methods. This framework functions as a simple decision tree and its utility is demonstrated using case examples. Determining a role for ABC transporters in insecticide resistance would help to shape future resistance management plans and guide the design of new insecticides.