Showing papers on "Circular dichroism published in 2019"
TL;DR: It is established that both chiral aggregates and just a few proteins in interparticle gaps of achiral assemblies are responsible for the ensemble signal, but single nanoparticles do not contribute.
Abstract: Plasmon-coupled circular dichroism has emerged as a promising approach for ultrasensitive detection of biomolecular conformations through coupling between molecular chirality and surface plasmons. Chiral nanoparticle assemblies without chiral molecules present also have large optical activities. We apply single-particle circular differential scattering spectroscopy coupled with electron imaging and simulations to identify both structural chirality of plasmonic aggregates and plasmon-coupled circular dichroism induced by chiral proteins. We establish that both chiral aggregates and just a few proteins in interparticle gaps of achiral assemblies are responsible for the ensemble signal, but single nanoparticles do not contribute. We furthermore find that the protein plays two roles: It transfers chirality to both chiral and achiral plasmonic substrates, and it is also responsible for the chiral three-dimensional assembly of nanorods. Understanding these underlying factors paves the way toward sensing the chirality of single biomolecules.
167 citations
TL;DR: In this paper, two sensing techniques based on the coordination chemistry of lanthanides are reviewed in detail, including circular dichroism (CD) spectroscopy and circular polarized luminescence (CPL).
99 citations
TL;DR: In this paper, ovalbumin (OVA) was phosphorylated under wet-heating in the presence of sodium tripolyphosphate at pH 6.0 and 60°C for 1, 2, 3, 4 and 5h, and the structural and physical properties of P-OVA were investigated.
91 citations
TL;DR: An overview about the most important experimental aspects of a VCD-based AC determination and the theoretical analysis are given and the comparison of experimental and computational spectra that leads to the final conclusion about the AC of the target molecules are described.
Abstract: Vibrational circular dichroism (VCD) spectroscopy is one of the most powerful techniques for the determination of absolute configurations (AC), as it does not require any specific UV/vis chromophor...
89 citations
TL;DR: In this article, the authors describe the latest progress and developments in experimental and theoretical studies of proteins using CD spectroscopy, including time-resolved measurements, oriented CD, and state-of-the-art experiments using polarized UV light from high-energy synchrotron radiation.
88 citations
TL;DR: The binding kinetics and affinity of LMF to HSA in the absence and presence of the amino acids were studies using stopped-flow circular dichroism and ITC techniques respectively that revealed that the bindig affinity and binding rate of the LMF-HSA interaction decreased in the presence of histidine, methionine and cysteine.
Abstract: The present study was designed to investigate the influence of two indispensable and two dispensable amino acids, including methionine, histidine, cysteine and proline, on the binding interaction between human serum albumin (HSA) and an antibiotic agent lomefloxacin (LMF). The fluorescence quenching experiments showed that the intrinsic emission of HSA was considerably quenched following binding to LMF in all the systems. Furthermore, in all the interactions the maximum wavelength of HSA was slightly decreased. The spectral changes observed in the binding systems we e all attributed to the alteration of the micro-environment around the tryptophan and tyrosine residues of HSA. The Kb values o HSA-LMF complex in the absence and presence of histidine, methionine, cysteine and proline have been obtained 6.02 × 105, 4.83 × 105, 5.05 × 105, 4.94 × 105 and 6.20 × 105 M-1 respectively. The various kind of Kb values showed the different interaction behavior between HSA and LMF in the absence and presence of amino acids mentioned. The data gathered by isothermal titration calorimetry (ITC) studies revealed that although all the binding interactions were exothermic, the amount of the heat exchanged during the HSA-LMF interaction increased in the presence of the amino acids especially cysteine. In the present study, the binding kinetics and affinity of LMF to HSA in the absence and presence of the amino acids were studies using stopped-flow circular dichroism and ITC techniques respectively. The results of these two techniques revealed that the bindig affinity and binding rate of the LMF-HSA interaction decreased in the presence of histidine, methionine and cysteine. In the presence of proline, the binding process of LMF-HSA was sped up and the affinity of LMF to HSA slightly increased. All the experimental results were then supported by the data collected from molecular modeling studies using density functional theory. Communicated by Ramaswamy H. Sarma.
80 citations
TL;DR: In this paper, the molecular binding mechanisms of two major soy protein fractions, β-conglycinin (7S) and glycinin-3-O-glucoside (C3G, a representative polyphenol in food), at pH 7.0 were explored.
79 citations
TL;DR: Benefiting from its strong chirality and spin-dependent transmission characteristics, the proposed folded metasurface may be applied to a range of novel photon-spin selective devices for optical communication technologies and biophotonics.
Abstract: Controlling the spin angular momentum of light (or circular polarization state) plays a crucial role in the modern photonic applications such as optical communication, circular dichroism spectroscopy, and quantum information processing. However, the conventional approaches to manipulate the spin of light require naturally occurring chiral or birefringent materials of bulky sizes due to the weak light–matter interactions. Here we experimentally demonstrate an approach to implement spin-selective transmission in the infrared region based on chiral folded metasurfaces that are capable of transmitting one spin state of light while largely prohibiting the other. Due to the intrinsic chirality of the folded metasurface, a remarkable circular dichroism as large as 0.7 with the maximum transmittance exceeding 92% is experimentally demonstrated. The giant circular dichroism is interpreted within the framework of charge-current multipole expansion. Moreover, the intrinsic chirality can be readily controlled by mani...
77 citations
TL;DR: Inspired by the natural stereoselectivity and the β-sheet structure, a series of d- and l-amino acid-modified polyoxometalate (POM) derivatives were synthesized, including positively charged amino acids and negatively charged and hydrophobic amino acids, to modulate Aβ aggregation.
Abstract: Due to the composed α-helical/β-strand structures, β-amyloid peptide (Aβ) is sensitive to chiral environments. The orientation and chirality of the Aβ strand strongly influence its aggregation. Aβ-formed fibrils have a cascade of chirality. Therefore, for selectively targeting amyloid aggregates, chirality preference can be one key issue. Inspired by the natural stereoselectivity and the β-sheet structure, herein, we synthesized a series of d- and l-amino acid-modified polyoxometalate (POM) derivatives, including positively charged amino acids (d-His and l-His) and negatively charged (d-Glu and l-Glu) and hydrophobic amino acids (d-Leu, l-Leu, d-Phe, and l-Phe), to modulate Aβ aggregation. Intriguingly, Phe-modified POMs showed a stronger inhibition effect than other amino acid-modified POMs, as evidenced by multiple biophysical and spectral assays, including fluorescence, circular dichroism, NMR, molecular dynamic simulations, and isothermal titration calorimetry. More importantly, d-Phe-modified POM had...
74 citations
TL;DR: Water-miscible ethylene glycol ethers are found to modify structure, dynamics, and reactivity of DNA by mechanisms possibly related to a biologically relevant hydrophobic catalysis and it is proposed that a modulated chemical potential of water can promote “longitudinal breathing” and the formation of unstacked holes while base unpairing is suppressed.
Abstract: Hydrophobic base stacking is a major contributor to DNA double-helix stability. We report the discovery of specific unstacking effects in certain semihydrophobic environments. Water-miscible ethylene glycol ethers are found to modify structure, dynamics, and reactivity of DNA by mechanisms possibly related to a biologically relevant hydrophobic catalysis. Spectroscopic data and optical tweezers experiments show that base-stacking energies are reduced while base-pair hydrogen bonds are strengthened. We propose that a modulated chemical potential of water can promote “longitudinal breathing” and the formation of unstacked holes while base unpairing is suppressed. Flow linear dichroism in 20% diglyme indicates a 20 to 30% decrease in persistence length of DNA, supported by an increased flexibility in single-molecule nanochannel experiments in poly(ethylene glycol). A limited (3 to 6%) hyperchromicity but unaffected circular dichroism is consistent with transient unstacking events while maintaining an overall average B-DNA conformation. Further information about unstacking dynamics is obtained from the binding kinetics of large thread-intercalating ruthenium complexes, indicating that the hydrophobic effect provides a 10 to 100 times increased DNA unstacking frequency and an “open hole” population on the order of 10−2 compared to 10−4 in normal aqueous solution. Spontaneous DNA strand exchange catalyzed by poly(ethylene glycol) makes us propose that hydrophobic residues in the L2 loop of recombination enzymes RecA and Rad51 may assist gene recombination via modulation of water activity near the DNA helix by hydrophobic interactions, in the manner described here. We speculate that such hydrophobic interactions may have catalytic roles also in other biological contexts, such as in polymerases.
73 citations
TL;DR: In this paper, a facile route to soft matter self-powered bulk heterojunction photodiode detectors sensitive to the circular polarization state of light is shown based on the intrinsic excitonic circular dichroism of the photoactive layer blend.
Abstract: A facile route to soft matter self-powered bulk heterojunction photodiode detectors sensitive to the circular polarization state of light is shown based on the intrinsic excitonic circular dichroism of the photoactive layer blend. As light detecting materials, enantiopure semiconducting small molecular squaraine derivates of opposite handedness are employed. Via Mueller matrix ellipsometry, the circular dichroism is proven to be of H-type excitonic nature and not originating from mesoscopic structural ordering. Within the green spectral range, the photodiodes convert circular polarized light into a handedness-dependent photocurrent with a maximum dissymmetry factor of ±0.1 corresponding to 5% overall efficiency for the polarization discrimination under short circuit conditions. On the basis of transfer matrix optical simulations, it is rationalized that the optical dissymmetry fully translates into a photocurrent dissymmetry for ease of device design. Thereby, the photodiode's ability to efficiently distinguish between left and right circularly polarized light without the use of external optical elements and voltage bias is demonstrated. This allows a straightforward and sustainable future design of flexible, lightweight, and compact integrated platforms for chiroptical imaging and sensing.
TL;DR: These unique hierarchical amplifications and memory of the macromolecular helicity in the copolymers by the covalent and further noncovalent chiral interactions are quantitatively explained on the basis of a linear Ising model.
Abstract: We report an unexpectedly strong amplification of the macromolecular helicity in dynamic helical copolymers of chiral/achiral and chiral/chiral ( R/ S) biphenylylacetylenes in which the chiral residues are remote from the biphenyl pendants and further from the main chains. The copolymers consisting of 20 mol % chiral monomers and chiral monomers of 20% enantiomeric excess (ee) showed a full induced circular dichroism as intense as that of the chiral homopolymer. In contrast, an analogous poly(phenylacetylene) bearing the identical chiral residue (100% ee) showed no circular dichroism in the polymer backbone, indicating the critical role of the biphenyl moieties in the observed high chiral amplification. As anticipated, the helix-sense excesses of the copolymer backbones composed of a small amount of chiral units (<20 mol %) and chiral units of low ee (<20%) were reduced. Interestingly, however, the macromolecular helicity of the copolymers was further drastically enhanced as a greater excess of a one-handed helix or inverted upon noncovalent interaction with nonracemic alcohols and subsequently retained (memorized) after complete removal of the chiral alcohol. Even in a polymer consisting of completely racemic repeating units, one-handed right- and left-handed helices could almost be induced and memorized. These unique hierarchical amplifications and memory of the macromolecular helicity in the copolymers by the covalent and further noncovalent chiral interactions are quantitatively explained on the basis of a linear Ising model.
TL;DR: Interestingly, a significant enhancement of circular dichronism (CD) and CPL signals of the L - 1 and D - 1 was observed by tuning the rotational speed of the mechanical stimulus, which implies that the chiral supramolecular polymerization was accelerated by the Mechanical stimulus.
Abstract: Finely controlled circularly polarized luminescence (CPL) supramolecular polymerization based on a tetraphenylethene core with four l- or d-alanine branch side chains (l-1 and d-1) in the solution state is presented, resulting from the tuning of mechanical stimulus. Weak, green emissions of l-1 and d-1 in tetrahydrofuran (THF) were converted into strong blue emissions by tuning the mechanical stimulus. The strong blue emissions were caused by an aggregation-induced emission (AIE) effect during the formation of a supramolecular polymer. Lag time in the supramolecular polymerization was drastically reduced by the mechanical stimulus, which was indicative of the acceleration of the supramolecular polymerization. A significant enhancement of circular dichroism (CD) and CPL signals of l-1 and d-1 was observed by tuning the rotational speed of the mechanical stimulus, implying that the chiral supramolecular polymerization was accelerated by the mechanical stimulus.
26 Apr 2019
TL;DR: Chiral enantiomeric amino acid Schiff base copper(II) complexes 1 and 2 (a and b) were synthesized and characterized by various spectroscopic techniques and showed the highest binding propensity possessing a rigid aromatic group in the amino acid framework.
Abstract: Chiral enantiomeric amino acid Schiff base copper(II) complexes 1 and 2 (a and b) were synthesized and characterized by various spectroscopic techniques (Fourier transform infrared, UV–vis, electron paramagnetic resonance, electrospray ionization-mass spectrometry, and circular dichroism) and single X-ray crystal diffraction analyses. To understand the selectivity and enantiomeric behavior of the complexes, binding interaction with ct-DNA and tRNA biomolecules was investigated by widely employed optical and hydrodynamic techniques. The binding experiments demonstrated that complexes 1 and 2 (a and b) interact strongly via the intercalative mode with preferential binding toward the tRNA biomolecule compared to ct-DNA. Furthermore, the order of binding propensity was 2a > 2b > 1a > 1b, implicating greater binding affinity of l-enantiomeric complexes, and complex 2a showed the highest binding propensity possessing a rigid aromatic group in the amino acid framework. Scanning electron microscopy analyses of co...
TL;DR: The interaction of Pyrogallol with human serum albumin (HSA) was investigated by UV, fluorescence, Circular dichroism, and molecular docking methods and indicated that PG induced conformational changes in the structure of HSA.
Abstract: In the present study, the interaction of Pyrogallol (PG) with human serum albumin (HSA) was investigated by UV, fluorescence, Circular dichroism (CD), and molecular docking methods. The results of ...
TL;DR: Polyphenols had impact on the structure and potential functionality of β-LG, which would be valuable in dairy processing industry and food nutrition security, and the polyphenol binding site directly obscures the IgE linear epitopes.
TL;DR: The concept of photothermal circular dichroism is experimentally realized, a technique that combines the enantioselective signal from circular dichROism with the high sensitivity ofPhotothermal microscopy, achieving a superior signal-to-noise ratio to detect chiral nano-objects.
Abstract: Circular dichroism (CD) spectroscopy is a powerful optical technique for the study of chiral materials and molecules. It gives access to an enantioselective signal based on the differential absorption of right and left circularly polarized light, usually obtained through polarization analysis of the light transmitted through a sample of interest. CD is routinely used to determine the secondary structure of proteins and their conformational state. However, CD signals are weak, limiting the use of this powerful technique to ensembles of many molecules. Here, we experimentally realize the concept of photothermal circular dichroism, a technique that combines the enantioselective signal from circular dichroism with the high sensitivity of photothermal microscopy, achieving a superior signal-to-noise ratio to detect chiral nano-objects. As a proof of principle, we studied the chiral response of single plasmonic nanostructures with CD in the visible range, demonstrating a signal-to-noise ratio better than 40 with only 30 ms integration time for these nanostructures. The high signal-to-noise ratio allows us to quantify the CD signal for individual nanoparticles. We show that we can distinguish relative absorption differences for right circularly and left circularly polarized light as small as gmin = 4 × 10-3 for a 30 ms integration time with our current experimental settings. The enhanced sensitivity of our technique extends CD studies to individual nano-objects and opens CD spectroscopy to numbers of molecules much lower than those in conventional experiments.
TL;DR: This study lays the foundations for the optimizations of new magnetically active organic chiral emitters with highly efficient chiral emissions according to the comparison of |glum| with their respective absorption anisotropy factors (|gabs|).
Abstract: Chiroptical properties of two chiral atropisomers of propeller-like trityl-based radical derivatives have been analyzed. A new absolute configuration (AC) assignment has been made, according to the combination of experimental and theoretical data. In this sense, their ACs have been determined through the comparison of the Cotton effects recorded by electronic circular dichroism (ECD) with the theoretical ECD of the open shell structures obtained by TD-DFT calculations. Finally, their circularly polarized luminescence (CPL) responses have been addressed. Remarkably, this is the first description of organic free radicals as intrinsic CPL emitters. Opposite signed CPL has been detected for each pair of conformers, with acceptable luminescent dissymmetry factors (|glum |≈0.5-0.8×10-3 ) considering their pure organic nature. In fact, highly efficient chiral emissions have been demonstrated, according to the comparison of |glum | with their respective absorption anisotropy factors (|gabs |). This pioneering study lays the foundations for the optimization of new magnetically active organic chiral emitters.
TL;DR: P pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1, an octa-peptide and double mutant of a naturally occurring β-strand peptide fragment of the protein Galectin-1 , available in bovine spleen is reported.
Abstract: Peptide-based hydrogels are highly promising for various biomedical applications owing to their precise self-assembly, biocompatibility, and sensitivity toward biologically relevant external stimuli. Herein, we report pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1. This is an octa-peptide and double mutant of a naturally occurring β-strand peptide fragment of the protein Galectin-1, available in bovine spleen. PEP-1 was synthesized by using the Rink amide resin as the solid support in a homemade apparatus. At pH 7.4, it exhibits spontaneous gelation with very high yield stress of 88.0 Pa and gel-to-sol temperature of 84 °C at C = 2.0 wt %. Microscopy studies revealed entangled fibrillar morphology whereas circular dichroism, Fourier tranform IR, and Thioflavin T assay indicated formation of β-sheet rich secondary structure. The assembled state was found to be stable in neutral pH whereas either decrease or increase in the pH resulted in disassembly owing to the presence of the pH responsive Asp and Lys residues. The gel network showed ability to entrap water-soluble guest molecules such as Calcein which could be selectively released at acidic pH whereas under neutral condition the release was negligible. MTT assay revealed remarkable biocompatibility of the PEP-1 gel as almost 100% cells were alive after 48 h incubation in the presence of PEP-1 (2.0 mg/mL).
20 Jan 2019
TL;DR: In this paper, a photoelastic modulator was employed to achieve shot-to-shot polarization switching of a 20-kHz pulse train of broadband femtosecond deep-UV pulses (250-370nm).
Abstract: The measurement of chirality and its temporal evolution are crucial for the understanding of a large range of biological functions and chemical reactions. Steady-state circular dichroism (CD) is a standard analytical tool for measuring chirality in chemistry and biology. Nevertheless, its push into the ultrafast time domain and in the deep-ultraviolet has remained a challenge, with only some isolated reports of subnanosecond CD. Here, we present a broadband time-resolved CD spectrometer in the deep ultraviolet (UV) spectral range with femtosecond time resolution. The setup employs a photoelastic modulator to achieve shot-to-shot polarization switching of a 20 kHz pulse train of broadband femtosecond deep-UV pulses (250–370 nm). The resulting sequence of alternating left- and right-circularly polarized probe pulses is employed in a pump-probe scheme with shot-to-shot dispersive detection and thus allows for the acquisition of broadband CD spectra of ground- and excited-state species. Through polarization scrambling of the probe pulses prior to detection, artifact-free static and transient CD spectra of enantiopure [Ru(bpy)3]2+ are successfully recorded with a sensitivity of <2×10−5 OD (≈0.7 mdeg). Due to its broadband deep-UV detection with unprecedented sensitivity, the measurement of ultrafast chirality changes in biological systems with amino-acid residues and peptides and of DNA oligomers is now feasible.
TL;DR: The stereoselective synthesis of a series of gigantic chiral Mo Blue POM clusters 1–5 that are formed by exploiting the synergy between coordinating lanthanides ions as symmetry breakers to produce MBs with chiral frameworks decorated with amino acids ligands that promote the selective formation of enantiopure MBs are reported.
Abstract: The synthesis of chiral polyoxometalates (POMs) is a challenge because of the difficulty to induce the formation of intrinsically chiral metal-oxo frameworks. Herein we report the stereoselective synthesis of a series of gigantic chiral Mo Blue (MB) POM clusters 1–5 that are formed by exploiting the synergy between coordinating lanthanides ions as symmetry breakers to produce MBs with chiral frameworks decorated with amino acids ligands; these promote the selective formation of enantiopure MBs. All the compounds share the same framework archetype, based on {Mo124Ce4}, which forms an intrinsically chiral Δ or Λ configurations, controlled by the configurations of functionalized chiral amino acids. The chirality and stability of 1–5 in solution are confirmed by circular dichroism, 1H NMR, and electrospray ion mobility–mass spectrometry studies. In addition, the framework of the {Mo124Ce4} MB not only behaves as a host able to trap a chiral {Mo8} cluster that is not accessible by traditional synthesis but als...
TL;DR: This work found that intermolecular hydrogen-bonding interactions between water (donor and acceptor) and N, N-dimethylformamide (DMF) as well as chloroform (CHCl3) and DMF could subtly alter the molecular packing and significantly affected the supramolecular self-assembled nanostructures and triggered circular dichroism (CD) signal reversal.
Abstract: Chiral nanostructures exhibited distinctive functions and attractive applications in complex biological systems, which demonstrated the subject of many outstanding research studies. In this work, various hierarchical composite film nanostructures were designed via supramolecular self-assembly using chiral amphiphilic glutamate derivatives and achiral porphyrin derivatives and their macroscopic enantioselective recognition properties were investigated. We have found that intermolecular hydrogen-bonding interactions between water (donor and acceptor) and N, N-dimethylformamide (DMF) as well as chloroform (CHCl3) (acceptor only) and DMF could subtly alter the molecular packing and significantly affected the supramolecular self-assembled nanostructures and triggered circular dichroism (CD) signal reversal. Present research work exemplified a feasible method to fabricate chiral flower-like and brick-like nanostructure films in different mixed solvents and large-scale chiral transfer from the molecular level to complex structures, which also provided a facile approach to identify certain l-/d-amino acids by means of contact angle detection using present obtained self-assembled composted films.
TL;DR: It is concluded that the chiroptical properties of QDs are dependent on the concentration and binding modes of the capping chiral ligands, and the design of advanced optically active nanomaterials is recommended.
Abstract: Chiroptically active fluorescent semiconductor nanocrystals, quantum dots (QDs), are of high interest from a theoretical and technological point of view, because they are promising candidates for a range of potential applications. Optical activity can be induced in QDs by capping them with chiral molecules, resulting in circular dichroism (CD) signals in the range of the QD ultraviolet-visible (UV-vis) absorption. However, the effects of the chiral ligand concentration and binding modes on the chiroptical properties of QDs are still poorly understood. In the present study, we report the strong influence of the concentration of a chiral amino acid (cysteine) on its binding modes upon the surface of CdSe/CdS QDs, resulting in varying QD chiroptical activity and corresponding CD signals. Importantly, we demonstrate that the increase of cysteine concentration is accompanied by the growth of the QD CD intensity, reaching a certain critical point, after which it starts to decrease. The intensity of the CD signal varies by almost an order of magnitude across this range. Nuclear magnetic resonance and Fourier transform infrared data, supported by density functional theory calculations, reveal a change in the binding mode of cysteine molecules from tridentate to bidentate when going from low to high concentrations, which results in a change in the CD intensity. Hence, we conclude that the chiroptical properties of QDs are dependent on the concentration and binding modes of the capping chiral ligands. These findings are very important for understanding chiroptical phenomena at the nanoscale and for the design of advanced optically active nanomaterials.
TL;DR: In this paper, temperature induced interactions between β-casein and ferulic acid were investigated under ultra-high temperature (UHT) conditions (140°C) utilising a variety of spectroscopic methods.
TL;DR: Observations indicated that ultrasound treatment was necessary for modification of CPP to meet the requirements for food processing, especially UCPP‐20, which showed a significant increase in antioxidant properties over CPP.
TL;DR: Overall, macrocyclization by hydrocarbon stapling appears to overcome the destabilization of α-helicity by helix breaking residues and, in the specific case of d-Trp7-modification, a highly potent ATSP-7041 analog was identified.
Abstract: Stapled α-helical peptides represent an emerging superclass of macrocyclic molecules with drug-like properties, including high-affinity target binding, protease resistance, and membrane permeability. As a model system for probing the chemical space available for optimizing these properties, we focused on dual Mdm2/MdmX antagonist stapled peptides related to the p53 N-terminus. Specifically, we first generated a library of ATSP-7041 (Chang et al., 2013) analogs iteratively modified by L-Ala and D-amino acids. Single L-Ala substitutions beyond the Mdm2/(X) binding interfacial residues (i.e., Phe3, Trp7, and Cba10) had minimal effects on target binding, α-helical content, and cellular activity. Similar binding affinities and cellular activities were noted at non-interfacial positions when the template residues were substituted with their d-amino acid counterparts, despite the fact that d-amino acid residues typically ‘break’ right-handed α-helices. d-amino acid substitutions at the interfacial residues Phe3 and Cba10 resulted in the expected decreases in binding affinity and cellular activity. Surprisingly, substitution at the remaining interfacial position with its d-amino acid equivalent (i.e., Trp7 to d-Trp7) was fully tolerated, both in terms of its binding affinity and cellular activity. An X-ray structure of the d-Trp7-modified peptide was determined and revealed that the indole side chain was able to interact optimally with its Mdm2 binding site by a slight global re-orientation of the stapled peptide. To further investigate the comparative effects of d-amino acid substitutions we used linear analogs of ATSP-7041, where we replaced the stapling amino acids by Aib (i.e., R84 to Aib4 and S511 to Aib11) to retain the helix-inducing properties of α-methylation. The resultant analog sequence Ac–Leu–Thr–Phe–Aib–Glu–Tyr–Trp–Gln–Leu–Cba–Aib–Ser–Ala–Ala–NH2 exhibited high-affinity target binding (Mdm2 Kd = 43 nM) and significant α-helicity in circular dichroism studies. Relative to this linear ATSP-7041 analog, several d-amino acid substitutions at Mdm2(X) non-binding residues (e.g., d-Glu5, d-Gln8, and d-Leu9) demonstrated decreased binding and α-helicity. Importantly, circular dichroism (CD) spectroscopy showed that although helicity was indeed disrupted by d-amino acids in linear versions of our template sequence, stapled molecules tolerated these residues well. Further studies on stapled peptides incorporating N-methylated amino acids, l-Pro, or Gly substitutions showed that despite some positional dependence, these helix-breaking residues were also generally tolerated in terms of secondary structure, binding affinity, and cellular activity. Overall, macrocyclization by hydrocarbon stapling appears to overcome the destabilization of α-helicity by helix breaking residues and, in the specific case of d-Trp7-modification, a highly potent ATSP-7041 analog (Mdm2 Kd = 30 nM; cellular EC50 = 600 nM) was identified. Our findings provide incentive for future studies to expand the chemical diversity of macrocyclic α-helical peptides (e.g., d-amino acid modifications) to explore their biophysical properties and cellular permeability. Indeed, using the library of 50 peptides generated in this study, a good correlation between cellular permeability and lipophilicity was observed.
TL;DR: The CD signal, around 220, 240 and 290 nm are opposite and symmetric, which conclusively demonstrates that l-CZDs and d-CQDs are enantiomers.
Abstract: Chiral carbon quantum dots (CQDs) with chirality, fluorescence and biocompatibility were synthesized by a one-step method with L-/D-tryptophan (L-/D-Trp), as both carbon source and chiral source. Levogyration-/dextrorotation-CQDs (L-/D-CQDs) were characterized by transmission electron microscopy, Fourier transform infrared spectrometry, ultraviolet-visible absorption, excitation and emission spectrometry and circular dichroism (CD) spectrometry. Results show that L-CQDs and D-CQDs present similar spherical morphology, functional groups and optical properties. The CD signal, around 220, 240 and 290 nm are opposite and symmetric, which conclusively demonstrates that L-CQDs and D-CQDs are enantiomers. Besides the CD signal around 220 nm from the inheritance of L-/D-Trp, two new chiral signals around 240 and 290 nm were induced by chiral environment.
TL;DR: This work employs DNA-templated strategies to control the chiral self-assembly of achiral chromophores with rationally tuned exciton transitions on gold nanosphere or gold nanorod surfaces to provide new insight into plasmonic CD enhancements and will inspire further studies on chiral light-matter interactions in strongly coupled plasMonic-excitonic systems.
Abstract: Circular dichroism (CD) from hybrid complexes of plasmonic nanostructures and chiral molecules has recently attracted significant interest. However, the hierarchical chiral self-assembly of molecul...
TL;DR: Concluding that encapsulation efficiency increased with hydrophobic content of the complexes providing insight for future work on the application of these materials for drug delivery, shows that the critical salt concentration, a key measure of PEC stability, increased with both increasing charge density as well as hydrophobicity.
Abstract: Polyelectrolyte complexation is a versatile platform for the design of self-assembled materials. Here we use rational design to create ionic hydrophobically-patterned peptides that allow us to precisely explore the role of hydrophobicity on electrostatic self-assembly. Polycations and polyanions were designed and synthesized with an alternating sequence of d- and l-chiral patterns of lysine or glutamic acid with either glycine, alanine or leucine due to their increasing hydrophobicity index, respectively. Two motifs were considered for the oppositely charged patterned peptides; one with equal residues of charged and uncharged amino acids and the other with increased charge density. Mass spectroscopy, circular dichroism, H- and F-NMR spectroscopy were used to characterize the polypeptides. Polyelectrolyte complexes (PECs) formed using the sequences were characterized using turbidity measurements, optical microscopy and infrared spectroscopy. Our results show that the critical salt concentration, a key measure of PEC stability, increased with both increasing charge density as well as hydrophobicity. Furthermore, by increasing the hydrophobicity, the amount of PEC formed increased with temperature, contrary to purely ionic PECs. Lastly, we assessed the encapsulation behavior of these materials using a hydrophobic dye. Concluding that encapsulation efficiency increased with hydrophobic content of the complexes providing insight for future work on the application of these materials for drug delivery.
TL;DR: A novel enantiopure bis-helicenic 2,2'-bipyridine system was prepared using a Negishi coupling, revealing efficient tuning of photophysical and chiroptical properties of the system.
Abstract: A novel enantiopure bis-helicenic 2,2'-bipyridine system was prepared using a Negishi coupling. Thanks to the bipyridine unit, the coordination with ZnII and protonation processes were studied revealing efficient tuning of photophysical (UV/Visible and emission) and chiroptical properties (electronic circular dichroism and circularly polarized emission) of the system. The coordination/decoordination and protonation/deprotonation processes appeared reversible thus constituting novel chiroptical switches.