A Synergistic Combinatorial and Chiroptical Study of Peptide Catalysts for Asymmetric Baeyer–Villiger Oxidation

Giuliano, Michael W.; Lin, Chung Yon; Romney, David K.; Miller, Scott J.; Anslyn, Eric V.

doi:10.1002/adsc.201500230

Cited by 39 publications

(19 citation statements)

References 47 publications

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“…Optical methods are compatible with parallel data acquisition, miniaturization, and multiwell plate formats and offer a new path to real high-throughput analysis of chiral samples 4–7 . Few examples of asymmetric reaction analysis with sensors operating on the principles of dynamic covalent chemistry 8–11 , metal complex coordination 12 , and supramolecular chemistry 13–15 to recognize a chiral target compound and to generate quantifiable ultraviolet (UV), fluorescence, and circular dichroism (CD) signals have been reported 16–18 . Comprehensive chirality sensing (CCS), i.e., determination of the absolute configuration, yield, and enantiomeric excess ( ee ), of crude asymmetric reaction mixtures via irreversible covalent product fixation has been largely neglected to date 19 .…”

Section: Introductionmentioning

confidence: 99%

Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures

2018

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Click reactions have become powerful synthetic tools with unique applications in the health and materials sciences. Despite the progress with optical sensors that exploit the principles of dynamic covalent chemistry, metal coordination or supramolecular assemblies, quantitative analysis of complex mixtures remains challenging. Herein, we report the use of a readily available coumarin conjugate acceptor for chiroptical click chirality sensing of the absolute configuration, concentration and enantiomeric excess of several compound classes. This method has several attractive features, including wide scope, fast substrate fixation without by-product formation or complicate equilibria often encountered in reversible substrate binding, excellent solvent compatibility, and tolerance of air and water. The ruggedness and practicality of this approach are demonstrated by comprehensive analysis of nonracemic monoamine samples and crude asymmetric imine hydrogenation mixtures without work-up. Click chemosensing addresses increasingly important time efficiency, cost, labor and chemical sustainability aspects and streamlines asymmetric reaction development at the mg scale.

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Section: Introductionmentioning

confidence: 99%

Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures

2018

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“…A number of polypeptides have been shown to promote protease-like reactions, utilizing specific folded conformations for controlling the catalytic activity.` 1 – 3 ] While simple shorter oligopeptides have been demonstrated to show the significant catalytic activity and selectivity,[ 4 , 5 ] intermediate length polypeptides (10–15 amino acids) generally do not lock in well-defined structures, limiting their catalytic performance. [ 1 , 6 , 7 ] Recently, there has been notable progress in developing polypeptides in this intermediate length range that carry out chemical reactions including hydrolysis and condensation as well as inorganic crystal growth by stabilizing the conformation for the catalysis with various electrostatic self-assembly strategies.…”

Section: Introductionmentioning

confidence: 99%

Molecular Self-Assembly Strategy for Generating Catalytic Hybrid Polypeptides

et al. 2016

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Recently, catalytic peptides were introduced that mimicked protease activities and showed promising selectivity of products even in organic solvents where protease cannot perform well. However, their catalytic efficiency was extremely low compared to natural enzyme counterparts presumably due to the lack of stable tertiary fold. We hypothesized that assembling these peptides along with simple hydrophobic pockets, mimicking enzyme active sites, could enhance the catalytic activity. Here we fused the sequence of catalytic peptide CP4, capable of protease and esterase-like activities, into a short amyloidogenic peptide fragment of Aβ. When the fused CP4-Aβ construct assembled into antiparallel β-sheets and amyloid fibrils, a 4.0-fold increase in the hydrolysis rate of p-nitrophenyl acetate (p-NPA) compared to neat CP4 peptide was observed. The enhanced catalytic activity of CP4-Aβ assembly could be explained both by pre-organization of a catalytically competent Ser-His-acid triad and hydrophobic stabilization of a bound substrate between the triad and p-NPA, indicating that a design strategy for self-assembled peptides is important to accomplish the desired functionality.

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“…9). 23 An opposite Cotton effect in the CD spectra of assembly 3 was observed for the same enantioenriched sample of DPHA as that for assembly 1 (Fig. 9).…”

Section: Resultsmentioning

confidence: 74%

From substituent effects to applications: enhancing the optical response of a four-component assembly for reporting ee values

et al. 2016

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High-throughput screening for asymmetric catalysts has stimulated an interest in optically-based enantiomeric-excess (ee) sensors, primarily for their improved time and cost efficiency when compared to the standard HPLC analysis. We present herein substituent-effect studies on a recently reported Zn(II) multicomponent assembly that is used for chiral, secondary alcohol ee detemination. The systematic altering of assemblies formed from select substituted pyridyl ligands pointed to the conclusion that steric effects dominate the mode of interaction at the pyridyl 3- and 6- positions. From these results we identified a new Zn(II)-centered multicomponent assembly with a higher dynamic range than previously reported. Calibration curves of the CD signals resulting from the new assembly led to an ee assay with a 1.7% error. To further the utility of the new assembly, a correlation was developed between alcohol substituent size to the respective enantiopure CD value.

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A Synergistic Combinatorial and Chiroptical Study of Peptide Catalysts for Asymmetric Baeyer–Villiger Oxidation

Cited by 39 publications

References 47 publications

Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures

Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures

Molecular Self-Assembly Strategy for Generating Catalytic Hybrid Polypeptides

From substituent effects to applications: enhancing the optical response of a four-component assembly for reporting ee values

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