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1.
Nano Lett ; 21(20): 8734-8740, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34623161

RESUMO

Although dry eye is highly prevalent, many challenges exist in diagnosing the symptom and related diseases. For this reason, anionic hydrogel-coated gold nanoshells (AuNSs) were used in the development of a label-free biosensor for detection of high isoelectric point tear biomarkers associated with dry eye. A custom, aldehyde-functionalized oligo(ethylene glycol)acrylate (Al-OEGA) was included in the hydrogel coating to enhance protein recognition through the formation of dynamic covalent (DC) imine bonds with solvent-accessible lysine residues present on the surface of select tear proteins. Our results demonstrated that hydrogel-coated AuNSs, composed of monomers that form ionic and DC bonds with select tear proteins, greatly enhance protein recognition due to changes in the maximum localized surface plasmon resonance wavelength exhibited by AuNSs in noncompetitive and competitive environments. Validation of the developed biosensor in commercially available pooled human tears revealed the potential for clinical translation to establish a method for dry eye diagnosis.


Assuntos
Síndromes do Olho Seco , Nanoconchas , Biomarcadores , Ouro , Humanos , Hidrogéis , Eletricidade Estática
2.
Environ Sci Technol ; 55(9): 5608-5619, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33881842

RESUMO

Extensive use of per- and polyfluoroalkyl substances (PFAS) has caused their ubiquitous presence in natural waters. One of the standard practices for PFAS removal from water is adsorption onto granular activated carbon (GAC); however, this approach generates a new waste stream, i.e., PFAS-laden GAC. Considering the recalcitrance of PFAS molecules in the environment, inadequate disposal (e.g., landfill or incineration) of PFAS-laden GAC may let PFAS back into the aquatic cycle. Therefore, developing approaches for PFAS-laden GAC management present unique opportunities to break its forever circulation within the aqueous environment. This comprehensive review evaluates the past two decades of research on conventional thermal regeneration of GAC and critically analyzes and summarizes the literature on regeneration of PFAS-laden GACs. Optimized thermal regeneration of PFAS-laden GACs may provide an opportunity to employ existing regeneration infrastructure to mineralize the adsorbed PFAS and recover the spent GAC. The specific objectives of this review are (i) to investigate the role of physicochemical properties of PFAS on thermal regeneration, (ii) to assess the changes in regeneration yield as well as GAC physical and chemical structure upon thermal regeneration, and (iii) to critically discuss regeneration parameters controlling the process. This literature review on the engineered regeneration process illustrates the significant promise of this approach that can break the endless environmental cycle of these forever chemicals, while preserving the desired physicochemical properties of the valuable GAC adsorbent.


Assuntos
Fluorcarbonetos , Poluentes Químicos da Água , Purificação da Água , Adsorção , Carvão Vegetal , Fluorcarbonetos/análise , Poluentes Químicos da Água/análise
3.
Molecules ; 25(21)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143109

RESUMO

The peroxidase activity of hemin-peptide complexes remains a potential factor in oxidative damage relevant to neurodegeneration. Here, we present the effect of temperature, ionic strength, and pH relevant to pathophysiological conditions on the dynamic equilibrium between high-spin and low-spin hemin-Aß40 constructs. This influence on peroxidase activity was also demonstrated using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and dopamine (DA) oxidation rate analyses with increasing ratios of Aß16 and Aß40 (up to 100 equivalents). Interaction and reactivity studies of aggregated Aß40-hemin revealed enhanced peroxidase activity versus hemin alone. Comparison of the results obtained using Aß16 and Aß40 amyloid beta peptides revealed marked differences and provide insight into the potential effects of hemin-Aß on neurological disease progression.


Assuntos
Peptídeos beta-Amiloides/química , Benzotiazóis/química , Dopamina/química , Hemina/química , Fragmentos de Peptídeos/química , Peroxidases/química , Ácidos Sulfônicos/química , Humanos , Oxirredução
4.
Chem Commun (Camb) ; 56(45): 6141-6144, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32364214

RESUMO

An aldehyde acrylate-based functional monomer was incorporated into poly(N-isopropylacrylamide-co-methacrylic acid) nanogels for use as protein receptors. The aldehyde component forms dynamic imines with surface exposed lysine residues, while carboxylic acid/carboxylate moieties form electrostatic interactions with high isoelectric point proteins. Together, these interactions effect protein adsorption and recognition.


Assuntos
Acrilamidas/química , Albuminas/química , Imunoglobulina G/química , Lactoferrina/química , Lactoglobulinas/química , Muramidase/química , Nanogéis/química , Ácidos Polimetacrílicos/química , Adsorção , Ponto Isoelétrico , Eletricidade Estática
5.
Chem ; 6(3): 703-724, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32201749

RESUMO

The complex etiology of neurodegeneration continues to stifle efforts to develop effective therapeutics. New agents elucidating key pathways causing neurodegeneration might serve to increase our understanding and potentially lead to improved treatments. Here, we demonstrate that a water-soluble manganese(II) texaphyrin (MMn) is a suitable magnetic resonance imaging (MRI) contrast agent for detecting larger amyloid beta constructs. The imaging potential of MMn was inferred on the basis of in vitro studies and in vivo detection in Alzheimer's disease C. elegans models via MRI and ICP-MS. In vitro antioxidant- and cellular-based assays provide support for the notion that this porphyrin analog shows promise as a therapeutic agent able to mitigate the oxidative and nitrative toxic effects considered causal in neurodegeneration. The present report marks the first elaboration of an MRI-active metalloantioxidant that confers diagnostic and therapeutic benefit in Alzheimer's disease models without conjugation of a radioisotope, targeting moiety, or therapeutic payload.

6.
J Am Chem Soc ; 142(8): 3913-3922, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32011873

RESUMO

Polymer topology dictates dynamic and mechanical properties of materials. For most polymers, topology is a static characteristic. In this article, we present a strategy to chemically trigger dynamic topology changes in polymers in response to a specific chemical stimulus. Starting with a dimerized PEG and hydrophobic linear materials, a lightly cross-linked polymer, and a cross-linked hydrogel, transformations into an amphiphilic linear polymer, lightly cross-linked and linear random copolymers, a cross-linked polymer, and three different hydrogel matrices were achieved via two controllable cross-linking reactions: reversible conjugate additions and thiol-disulfide exchange. Significantly, all the polymers, before or after topological changes, can be triggered to degrade into thiol- or amine-terminated small molecules. The controllable transformations of polymeric morphologies and their degradation herald a new generation of smart materials.


Assuntos
Hidrogéis/química , Polímeros/química , Química Click , Reagentes para Ligações Cruzadas/química , Dimerização , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular
7.
Angew Chem Int Ed Engl ; 58(1): 74-85, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30098086

RESUMO

Dynamic assembly of macromolecules in biological systems is one of the fundamental processes that facilitates life. Although such assembly most commonly uses noncovalent interactions, a set of dynamic reactions involving reversible covalent bonding is actively being exploited for the design of functional materials, bottom-up assembly, and molecular machines. This Minireview highlights recent implementations and advancements in the area of tunable orthogonal reversible covalent (TORC) bonds for these purposes, and provides an outlook for their expansion, including the development of synthetically encoded polynucleotide mimics.


Assuntos
Substâncias Macromoleculares/química , Humanos , Estrutura Molecular
8.
New J Chem ; 42(11): 8577-8582, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-30386131

RESUMO

A synthetic peptide containing two Nε-methyl lysines (Ac-K(Nε-Me)GYTGYTGK(Nε-Me)D-OH) was alkylated with bipyridine (bipy) ligands substituted at the fifth (MP-5) and sixth (MP-6) positions, thereby creating Ac-K(Nε-Me, Nε-Bipy)GYTGYTGK(Nε-Me, Nε-Bipy)D-OH. Peptides with 6-position bipyridine did not bind to Fe2+ and Zn2+. Peptides with 5-position bipyridine bound these metals, and in the presence of one equivalent of a free bipy derivative folded into a macrocycle. Further, the free bipy derivative could also contain a cyclized peptide derived from hydrazone formation, resulting in complex but controlled quaternary peptide structure.

9.
J Am Chem Soc ; 140(10): 3768-3774, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29466660

RESUMO

Peptide oligomers offer versatile scaffolds for the formation of potent antimicrobial agents due to their high sequence versatility, inherent biocompatibility, and chemical tunability. Though many methods exist for the formation of peptide-based macrocycles (MCs), increasingly pervasive in commercial antimicrobial therapeutics, the introduction of multiple looped structures into a single peptide oligomer remains a significant challenge. Herein, we report the utilization of dynamic hydrazone condensation for the versatile formation of single-, double-, and triple-loop peptide MCs using simple dialdehyde or dihydrazide small-molecule cross-linkers, as confirmed by MALDI-TOF MS, HPLC, and SDS-PAGE. Furthermore, incorporation of aldehyde-containing side chains onto peptides synthesized from hydrazide C-terminal resins resulted in tunable peptide MC assemblies formed directly upon resin cleavage post solid-phase peptide synthesis. Both of these types of dynamic covalent assemblies produced significant enhancements to overall antimicrobial properties when introduced into a known antimicrobial peptide, buforin II, when compared to the original unassembled sequence.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Sequência de Aminoácidos , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Técnicas de Química Sintética/métodos , Humanos , Compostos Macrocíclicos/síntese química , Peptídeos/síntese química , Proteínas/farmacologia
10.
Nat Chem ; 10(1): 45-50, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-29256509

RESUMO

Naturally occurring peptides and proteins often use dynamic disulfide bonds to impart defined tertiary/quaternary structures for the formation of binding pockets with uniform size and function. Although peptide synthesis and modification are well established, controlling quaternary structure formation remains a significant challenge. Here, we report the facile incorporation of aryl aldehyde and acyl hydrazide functionalities into peptide oligomers via solid-phase copper-catalysed azide-alkyne cycloaddition (SP-CuAAC) click reactions. When mixed, these complementary functional groups rapidly react in aqueous media at neutral pH to form peptide-peptide intermolecular macrocycles with highly tunable ring sizes. Moreover, sequence-specific figure-of-eight, dumbbell-shaped, zipper-like and multi-loop quaternary structures were formed selectively. Controlling the proportions of reacting peptides with mismatched numbers of complementary reactive groups results in the formation of higher-molecular-weight sequence-defined ladder polymers. This also amplified antimicrobial effectiveness in select cases. This strategy represents a general approach to the creation of complex abiotic peptide quaternary structures.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Cíclicos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Aldeídos/síntese química , Alcinos/química , Sequência de Aminoácidos , Antibacterianos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Azidas/química , Química Click , Reação de Cicloadição , Hidrazinas/síntese química , Peptídeos Cíclicos/síntese química , Pseudomonas aeruginosa/efeitos dos fármacos , Compostos de Amônio Quaternário/síntese química , Staphylococcus aureus/efeitos dos fármacos
11.
New J Chem ; 41(1): 126-133, 2017 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-28649175

RESUMO

Current approaches for incorporating boronic acids into peptides require one of the following: the synthesis of commercially unavailable pinacol-protected boronate ester amino acid building blocks, amidation of small-molecule amine-containing boronic acids, or reductive amination of amine residues with 2-formylphenyl boronic acid. These methods have drawbacks, such as the use of excess starting materials, the lack of reactive-site specificity, or the inability to add multiple boronic acids in solution. In addition, several of these approaches do not allow for incorporation of the critical o-aminomethyl functionality that allows for binding of sacharrides under physiological conditions. In this work, we report three methods to functionalize synthetic peptides with boronic acids using solid-phase and solution-phase chemistries by alkylating a secondary amine with o-(bromomethyl)phenylboronic acid. Solution-phase chemistries afforded the highest yields, and were used to synthesize seven complex biotinylated multi-boronic acid peptides.

12.
Chemistry ; 23(16): 3903-3909, 2017 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-28117920

RESUMO

The G-class nerve agents, which include sarin, soman, and cyclosarin, react readily with nucleophilic reagents to produce fluoride. Thus, a chemosensing protocol has been designed for these agents that pairs the nucleophilic reactivity of oximates for generating fluoride with an autoinductive target amplification reaction to amplify the quantity of fluoride for facile colorimetric and fluorescent optical quantification. The chemosensing protocol was demonstrated by using the nerve agent surrogate diisopropyl fluorophosphate (DFP) and benzaldoxime as the nucleophile. Autoinductive fluoride amplification responds to fluoride released from DFP by amplifying the fluoride concentration and a yellow reporter molecule. The reporter is a conjugated oligomer with a nominal repeating unit that originates from 4-aminobenzaldehyde. Exposure of the amplified fluoride to a fluoride-specific ratiometric fluorescent reporter provides a fluorescent readout, in which three fluorophores are generated per fluoride. Both colorimetric and fluorescent readouts enable quantitative assays with low micromolar limits of detection for fluoride resulting from DFP. More importantly, this work demonstrates the successful merging of multiple complex reactions for achieving selective, sensitive, and quantitative chemosensing.


Assuntos
Colorimetria/métodos , Fluoretos/análise , Isoflurofato/análise , Agentes Neurotóxicos/análise , Espectrometria de Fluorescência/métodos , Corantes Fluorescentes/química , Compostos Organofosforados/análise , Oximas/química , Fosfatos/análise , Sarina/análise , Soman/análise
13.
Phys Chem Chem Phys ; 16(23): 11456-60, 2014 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-24800924

RESUMO

The specific conformational states responsible for the unique, reversible temperature- and solvent-driven chiroptical switching process experienced by poly(N-1-naphthyl-N'-octadecyl-carbodiimide) (PNOC) have been identified using VCD spectroscopy and DFT calculations. The distinct VCD spectra of PNOC corresponding to the two specific conformations were obtained for the polymer dissolved in DCM-d2 (state A) and CDCl3 (predominantly state B). To specifically assign the structures of both conformations, two simplified 7mer models were constructed and optimized using DFT calculations. The theoretical spectra associated with these model conformations show a high level of agreement when compared to the experimental VCD spectra. The two states consist of the naphthyl pendant groups aligned directionally opposing the helical rotation (model A) and aligned with the helicity of the backbone (model B). This pendant reorientation causes very large OR and ECD Cotton effect inversions upon modification to the temperature or solvent composition of dilute (+)-PNOC solutions in specific solvents. In addition, the pendant group equilibrium from state A to B causes a contraction of the helical pitch from the more expanded 5/1 pitch to the more contracted 7/2 pitch resulting in increased disorder of the solvation sphere surrounding the polymer chain.

14.
J Am Chem Soc ; 135(51): 19292-303, 2013 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-24313274

RESUMO

The thermo- and solvo-driven chiroptical switching process observed in specific polycarbodiimides occurs in a concerted fashion with large deviations in specific optical rotation (OR) and CD Cotton effect as a consequence of varying populations of two distinct polymer conformations. These two conformations are clearly visible in the (15)N NMR and IR spectra of the (15)N-labeled poly((15)N-(1-naphthyl)-N'-octadecylcarbodiimide) (Poly-3) and poly((15)N-(1-naphthyl)-(15)N'-octadecylcarbodiimide) (Poly-5). Using van't Hoff analysis, the enthalpies and entropies of switching (ΔHswitching; ΔSswitching) were calculated for both Poly-3 and Poly-5 using the relative integrations of both peaks in the (15)N NMR spectra at different temperatures to measure the populations of each state. The chiroptical switching (i.e., transitioning from state A to state B) was found to be an endothermic process (positive ΔHswitching) for both Poly-3 and Poly-5 in all solvents studied, meaning the conformation correlating with the downfield chemical shift (ca. 148 ppm, state B) is the higher enthalpy state. The compensating factor behind this phenomenon has been determined to be the large increase in entropy in CHCl3 as a result of the switching. Herein, we propose that the increased entropy in the system is a direct consequence of increased disorder in the solvent as the switching occurs. Specifically, the chloroform solvent molecules are very ordered around the polymer chains due to favorable solvent-polymer interactions, but as the switching occurs, these interactions become less favorable and disorder results. The same level of solvent disorder is not achieved in toluene, causing the chiroptical switching process to occur at higher temperatures.

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