Disulfide-Mediated Reversible Polymerization toward Intrinsically Dynamic Smart Materials

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(5), P. 2022 - 2033

Published: Jan. 6, 2022

The development of a dynamic chemistry toolbox to endow materials behavior has been key the rational design future smart materials. rise supramolecular and covalent offers many approaches construction polymers that can adapt, respond, repair, recycle. Within this toolbox, building blocks based on 1,2-dithiolanes have become an important scaffold, featuring their reversible polymerization mediated by disulfide bonds, which enables unique class at intersection adaptable networks. This Perspective aims explore as versatile structural unit for summarizing state art well providing overview fundamental challenges involved in research area its potential directions.

Language: Английский

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The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7782 - 7853

Published: May 15, 2023

The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, basic research. A plethora chemical genetic approaches been devised to make accessible more "undruggable" targets equipped with new functions illustrating or regulating biological processes precisely. In this Review, addition introducing how naked various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide antibody-enzyme etc.) work therapeutic applications, special attention has paid chemistry tools helped optimize the outcome (i.e., enhanced efficacy reduced side effects) facilitate multifunctionalization antibodies, focus on emerging fields such targeted protein degradation, real-time live-cell imaging, catalytic labeling decaging spatiotemporal control well engagement inside cells. With advances modern biotechnology, well-designed derivatives via size miniaturization together efficient delivery systems emerged, which gradually improved our understanding important paved way pursue novel for potential treatments diseases.

Language: Английский

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Asymmetric Synthesis of S(IV) and S(VI) Stereogenic Centers

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 700 - 714

Published: Feb. 28, 2023

Sulfur can form diverse S(IV) and S(VI) stereogenic centers, of which some have gained significant attention recently due to their increasing use as pharmacophores in drug discovery programs. The preparation these sulfur centers enantiopure has been challenging, progress made will be discussed this Perspective. This Perspective summarizes different strategies, with selected works, for asymmetric synthesis moieties, including diastereoselective transformations using chiral auxiliaries, enantiospecific compounds, catalytic enantioselective synthesis. We discuss the advantages limitations strategies provide our views on how field develop.

Language: Английский

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Biosynthesis and genetic encoding of activated nitriles for fast protein conjugation and tunable fluorogenic labeling

Chem, Journal Year: 2025, Volume and Issue: unknown, P. 102385 - 102385

Published: Jan. 1, 2025

Language: Английский

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Oligonucleotide Phosphorothioates Enter Cells by Thiol‐Mediated Uptake

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(35), P. 19102 - 19106

Published: June 26, 2021

Oligonucleotide phosphorothioates (OPS) are DNA or RNA mimics where one phosphate oxygen is replaced by a sulfur atom. They have been shown to enter mammalian cells much more efficiently than non-modified DNA. Thus, solving of the key challenges with oligonucleotide technology, OPS became very useful in practice, several FDA-approved drugs on market late clinical trials. However, mechanism accounting for this facile cellular uptake unknown. Here, we show that thiol-mediated uptake. The transient adaptive network produced dynamic covalent pseudo-disulfide exchange characterized action. Inhibitors nanomolar efficiency provided, together activators reduce endosomal capture efficient delivery into cytosol, site

Language: Английский

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From quantum‐derived principles underlying cysteine reactivity to combating the COVID‐19 pandemic

Wiley Interdisciplinary Reviews Computational Molecular Science, Journal Year: 2022, Volume and Issue: 12(5)

Published: March 5, 2022

The COVID-19 pandemic poses a challenge in coming up with quick and effective means to counter its cause, the SARS-CoV-2. Here, we show how key factors governing cysteine reactivity proteins derived from combined quantum mechanical/continuum calculations led novel multi-targeting strategy against SARS-CoV-2, contrast developing potent drugs/vaccines single viral target such as spike protein. Specifically, they discovery of reactive cysteines evolutionary conserved Zn

Language: Английский

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Thiol‐Disulfide Exchange as a Route for Endosomal Escape of Polymeric Nanoparticles

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(37)

Published: July 22, 2022

Endosomal entrapment has remained the major bottleneck for cytosolic delivery of nanoparticle-based systems. Uncovering fundamentally new pathways endosomal escape is therefore highly sought. Herein, we report that disulfide bonds can enhance through contacts with cellular exofacial thiols, in addition to facilitating uptake. Our results are supported comparative analysis polymeric nanogels variable accessibility by placing these functionalities at core or shell nanogels. The findings here inform future chemical design vehicles.

Language: Английский

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Controllable Disulfide Exchange Polymerization of Polyguanidine for Effective Biomedical Applications by Thiol‐Mediated Uptake

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(23)

Published: March 19, 2022

Abstract New preparation methods of vectors are the key to developing next generation biomacromolecule delivery systems. In this study, a controllable disulfide exchange polymerization was established obtain low‐toxicity and efficient bioreducible polyguanidines (mPEG 225 ‐ b ‐PSS n , =13, 26, 39, 75, 105) by regulating concentration activated nucleophiles reaction time under mild conditions. The relationship between degrees biocompatibility studied identify optimal polyguanidine mPEG 26 . Such exhibited good in vitro performance delivering different functional nucleic acids. impressive therapeutic effects were further verified 4T1 tumor‐bearing mice as well with full‐thickness skin defects. Controllable provides an attractive strategy for construction new

Language: Английский

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Efficient delivery of a DNA aptamer-based biosensor into plant cells for glucose sensing through thiol-mediated uptake

Science Advances, Journal Year: 2022, Volume and Issue: 8(26)

Published: June 29, 2022

DNA aptamers have been widely used as biosensors for detecting a variety of targets. Despite decades success, they not applied to monitor any targets in plants, even though plants are major platform providing oxygen, food, and sustainable products ranging from energy fuels chemicals, high-value such pharmaceuticals. A barrier progress is lack efficient methods deliver into plant cells. We herein report thiol-mediated uptake method that more efficiently delivers Arabidopsis tobacco leaf cells than another state-of-the-art method, nanostructures. Such allowed delivery glucose aptamer sensor sensing glucose. This demonstration opens new avenue apply sensors functional studies various targets, including metabolites, hormones, metal ions, proteins better understanding the biodistribution regulation these species their functions.

Language: Английский

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Covalent conjugation and non-covalent complexation strategies for intracellular delivery of proteins using cell-penetrating peptides

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116910 - 116910

Published: June 8, 2024

Therapeutic proteins provided new opportunities for patients and high sales volumes. However, they are formulated extracellular targets. The lipophilic barrier of the plasma membrane renders vast array intracellular targets out reach. Peptide-based delivery systems, namely cell-penetrating peptides (CPPs), have few safety concerns, low immunogenicity, with control over administered doses. This study investigates CPP-based protein systems by classifying them into CPP-protein "covalent conjugation" CPP: "non-covalent complexation" categories. Covalent conjugates ensure proximity CPP to cargo, which can improve cellular uptake endosomal escape. We will discuss various aspects covalent through non-cleavable (stable) or cleavable bonds. Non-cleavable produced recombinant DNA technology express complete fusion in a host cell chemical ligation protein, ensures stability during process. bonds classified pH-sensitive redox-sensitive bonds, enzyme-cleavable physical stimuli linkers (light radiation, ultrasonic waves, thermo-responsive). highlighted key characteristics non-covalent complexes electrostatic hydrophobic interactions preserve conformational integrity cargo. CPP-mediated complexation, such as zippers, adaptor methods, avidin-biotin technology, featured. Conclusively, complexation methods appropriate when number samples be screened. In contrast, biological activity is critical compartment, conjugation protocols preferred.

Language: Английский

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