12 research outputs found
Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets.
The ability of antibodies to bind a wide variety of analytes with high specificity and high affinity makes them ideal candidates for therapeutic and diagnostic applications. However, the poor stability and high production cost of antibodies have prompted exploration of a variety of synthetic materials capable of specific molecular recognition. Unfortunately, it remains a fundamental challenge to create a chemically diverse population of protein-like, folded synthetic nanostructures with defined molecular conformations in water. Here we report the synthesis and screening of combinatorial libraries of sequence-defined peptoid polymers engineered to fold into ordered, supramolecular nanosheets displaying a high spatial density of diverse, conformationally constrained peptoid loops on their surface. These polyvalent, loop-functionalized nanosheets were screened using a homogeneous Förster resonance energy transfer (FRET) assay for binding to a variety of protein targets. Peptoid sequences were identified that bound to the heptameric protein, anthrax protective antigen, with high avidity and selectivity. These nanosheets were shown to be resistant to proteolytic degradation, and the binding was shown to be dependent on the loop display density. This work demonstrates that key aspects of antibody structure and function-the creation of multivalent, combinatorial chemical diversity within a well-defined folded structure-can be realized with completely synthetic materials. This approach enables the rapid discovery of biomimetic affinity reagents that combine the durability of synthetic materials with the specificity of biomolecular materials
Computational and Experimental Evidence of Emergent Equilibrium Isotope Effects in Anion Receptor Complexes
Computational and Experimental Evidence of Emergent Equilibrium Isotope Effects in Anion Receptor Complexes
The measurement of a deuterium equilibrium
isotope effect (EIE)
for the aryl CH···Cl<sup>–</sup> interaction
of anion receptor <b>1H/1D</b> is reported. Computations corroborate
the results of solution measurements for a small, normal EIE in the
full complex (<i>K</i><sub>a</sub><sup>H</sup>/<i>K</i><sub>a</sub><sup>D</sup> = 1.019 ± 0.010). Interestingly,
isotope effects involving fragments of the anion receptor (urea, aryl
ring, etc.) are predicted to produce an inverse effect. This points
to an unusual and subtle structural organization effect of the anion
receptor complex that changes the nature of the combined interactions
to a normal isotope effect. The reversal of EIE values suggests that
overall architecture of the anion receptor can dramatically impact
the nature of bonding in these complexes
Computational and Experimental Evidence of Emergent Equilibrium Isotope Effects in Anion Receptor Complexes
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A Synthetic Supramolecular Receptor for the Hydrosulfide Anion
A Contemporary Review of the Treatment Landscape and the Role of Predictive and Prognostic Biomarkers in Pancreatic Adenocarcinoma
Pancreatic cancer continues to represent one of the leading causes of cancer-related morbidity and mortality in the developed world. Over the past decade, novel systemic therapy combination regimens have contributed to clinically meaningful and statistically significant improvements in overall survival as compared to conventional monotherapy. However, the prognosis for most patients remains guarded secondary to the advanced stages of disease at presentation. There is growing consensus that outcomes can be further optimized with the use of predictive and prognostic biomarkers whereby the former can be enriching for patients who would benefit from therapies and the latter can inform decision-making regarding the need and timing of advanced care planning. One of the challenges of current biomarkers is the lack of standardization across clinical practices such that comparability between jurisdictions can be difficult or even impossible. This inconsistency can impede widespread implementation of their use. In this review article, we provide a comprehensive overview of the contemporary treatment options for pancreatic cancer and we offer some insights into the existing landscape and future directions of biomarker development for this disease
Substituent Effects in CH Hydrogen Bond Interactions: Linear Free Energy Relationships and Influence of Anions
Substituent Effects in CH Hydrogen Bond Interactions: Linear Free Energy Relationships and Influence of Anions
Aryl
CH hydrogen bonds (HBs) are now commonly recognized as important
factors in a number of fields, including molecular biology, stereoselective
catalysis, and anion supramolecular chemistry. As the utility of CH
HBs has grown, so to has the need to understand the structure–activity
relationship for tuning both their strength and selectivity. Although
there has been significant computational effort in this area, an experimental
study of the substituent effects on CH HBs has not been previously
undertaken. Herein we disclose a systematic study of a single CH HB
by using traditional urea donors as directing groups in a supramolecular
binding cavity. Experimentally determined association constants are
examined by a combination of computational (electrostatic potential)
and empirical (σ<sub>m</sub> and σ<sub>p</sub>) values
for substituent effects. The dominance of electrostatic parameters,
as observed in a computational DFT study, is consistent with current
CH HB theory; however, a novel anion dependence of the substituent
effects is revealed in solution
Conducting research at primarily undergraduate institutions
Undergraduate research and education are critical parts of the scientific ecosystem. Professors at primarily undergraduate institutions (PUIs) bear responsibility for molding young scientists while carrying out high quality research. In this Voices piece, researchers offer inspiring replies to the following prompt: in your role as a professor, what are the challenges and opportunities when conducting research at a PUI