keyword
https://read.qxmd.com/read/37955377/a-dual-mechanism-targeted-bioorthogonal-prodrug-therapy
#21
JOURNAL ARTICLE
Qingxin Yao, Feng Lin, Chenghao Lu, Ruijia Zhang, Hanlin Xu, Xiaoqian Hu, Ziyang Wu, Yuan Gao, Peng R Chen
Bioorthogonal prodrug therapies offer an intriguing two-component system that features enhanced circulating stability and controlled activation on demand. Current strategies often deliver either the prodrug or its complementary activator to the tumor with a monomechanism targeted mechanism, which cannot achieve the desired antitumor efficacy and safety profile. The orchestration of two distinct and orthogonal mechanisms should overcome the hierarchical heterogeneity of solid tumors to improve the delivery efficiency of both components simultaneously for bio-orthogonal prodrug therapies...
November 13, 2023: Bioconjugate Chemistry
https://read.qxmd.com/read/37933960/analysis-of-cdpk1-targets-identifies-a-trafficking-adaptor-complex-that-regulates-microneme-exocytosis-in-toxoplasma
#22
JOURNAL ARTICLE
Alex W Chan, Malgorzata Broncel, Eden Yifrach, Nicole R Haseley, Sundeep Chakladar, Elena Andree, Alice L Herneisen, Emily Shortt, Moritz Treeck, Sebastian Lourido
Apicomplexan parasites use Ca2+ -regulated exocytosis to secrete essential virulence factors from specialized organelles called micronemes. Ca2+ -dependent protein kinases (CDPKs) are required for microneme exocytosis; however, the molecular events that regulate trafficking and fusion of micronemes with the plasma membrane remain unresolved. Here, we combine sub-minute resolution phosphoproteomics and bio-orthogonal labeling of kinase substrates in Toxoplasma gondii to identify 163 proteins phosphorylated in a CDPK1-dependent manner...
November 7, 2023: ELife
https://read.qxmd.com/read/37906440/glutathione-mediates-control-of-dual-differential-bio-orthogonal-labelling-of-biomolecules
#23
JOURNAL ARTICLE
Frederik Peschke, Andrea Taladriz-Sender, Matthew J Andrews, Allan J B Watson, Glenn Burley
Traditional approaches to bio-orthogonal reaction discovery have focused on developing reagent pairs that react faster with each other than their metabolic degradation. Glutathione (GSH) is typically responsible for the deactivation of most bio-orthogonal reagents. Here we demonstrate that GSH promotes a Cu-catalysed (3+2) cycloaddition reaction between an ynamine and an azide. We show that GSH acts as a redox modulator to control the Cu oxidation state in these cycloadditions. Rate enhancement of this reaction is specific for ynamine substrates and is tuneable by the Cu:GSH ratio...
October 31, 2023: Angewandte Chemie
https://read.qxmd.com/read/37866014/bio-orthogonal-engineered-peptide-a-multi-functional-strategy-for-the-gene-therapy-of-osteoporotic-bone-loss
#24
JOURNAL ARTICLE
Wei Wang, Qing Wang, Lei Yu, Gaoran Ge, Xin Liu, Ang Gao, Guomin Wang, Zhengwei Wu, Jiaxiang Bai, Huaiyu Wang, Paul K Chu, Dechun Geng
Osteoporosis is a degenerative disease affecting millions of elderly people globally and increases the risk of bone fractures due to the reduced bone density. Drugs are normally prescribed to treat osteoporosis, especially after surgical treatment of osteoporotic fractures. However, many anti-osteoporotic drugs produce deleterious side effects. The recent development of gene therapy utilizing oligonucleotides (ONs) has spurred the development of new therapies for osteoporosis. Nevertheless, most ONs lack the capability of cell penetration and lysosome escape and hence, intracellular delivery of ON remains a challenge...
October 13, 2023: Biomaterials
https://read.qxmd.com/read/37839142/a-bifunctional-agent-for-efficient-imaging-of-pd-l1-and-antimelanoma-activity
#25
JOURNAL ARTICLE
Jin Wang, Xiaoyan Pan, Ping Hai, Yongbiao Zheng, Jie Zhang, Yuanyuan Shan
Immune checkpoint inhibitors targeting PD-L1 lead to challenging patterns of efficacy and toxicity. Herein, by focusing on tracing the molecular biomarker of response to efficacy, we formulated a central hypothesis for the construction of theranostic functional monoclonal antibody incorporation with tracing ability based on fluorescence turn-on and controllable release strategies. Functional atezolizumab was constructed by in situ assembly of both biorthogonal group and controllable release group. The theranostic monoclonal antibodies achieved quantitative monitoring of PD-L1 on cells with different expression levels through biorthogonal light-up fluorescence, followed by the release of atezolizumab in combination with high tumor reduction conditions to promote immune activation...
October 11, 2023: Bioorganic Chemistry
https://read.qxmd.com/read/37835538/a-novel-allogeneic-rituximab-conjugated-gamma-delta-t-cell-therapy-for-the-treatment-of-relapsed-refractory-b-cell-lymphoma
#26
JOURNAL ARTICLE
Hao-Kang Li, Tai-Sheng Wu, Yi-Chiu Kuo, Ching-Wen Hsiao, Hsiu-Ping Yang, Chia-Yun Lee, Pei-Ju Leng, Yun-Jung Chiang, Zih-Fei Cheng, Sen-Han Yang, Yan-Liang Lin, Li-Yu Chen, Ciao-Syuan Chen, Yu-Ju Chen, Shih-Chia Hsiao, Sai-Wen Tang
Chimeric antigen receptor T cell (CAR-T) therapy has been applied in the treatment of B-cell lymphoma; however, CAR-T manufacturing requires virus- or non-virus-based genetic modification, which causes high manufacturing costs and potential safety concerns. Antibody-cell conjugation (ACC) technology, which originated from bio-orthogonal click chemistry, provides an efficient approach for arming immune cells with cancer-targeting antibodies without genetic modification. Here, we applied ACC technology in Vγ9Vδ2 T (γδ2 T) cells to generate a novel off-the-shelf CD20-targeting cell therapy ACE1831 (rituximab-conjugated γδ2 T cells) against relapsed/refractory B-cell lymphoma...
October 4, 2023: Cancers
https://read.qxmd.com/read/37821742/expanding-the-range-of-bio-orthogonal-tags-for-multiplex-stimulated-raman-scattering-microscopy
#27
JOURNAL ARTICLE
William Tipping, Neville Murphy, Henry Braddick, Liam Wilson, Nicholas Tomkinson, Karen Faulds, Duncan Graham, Pau Farras Costa
Multiplex optical detection in live cells is challenging due to overlapping signals and poor signal-to-noise associated with some chemical reporters. To address this, the application of spectral phasor analysis to stimulated Raman scattering (SRS) microscopy for unmixing three bio-orthogonal Raman probes within cells is reported. Triplex detection of a metallacarborane using the B-H stretch at 2480- 2650 cm-1 , together with a bis-alkyne and deuterated fatty acid can be achieved within the cell-silent region of the Raman spectrum...
October 11, 2023: Angewandte Chemie
https://read.qxmd.com/read/37795828/engineered-small-extracellular-vesicle-mediated-nox4-sirna-delivery-for-targeted-therapy-of-cardiac-hypertrophy
#28
JOURNAL ARTICLE
Ji-Young Kang, Dasom Mun, Yumin Chun, Da-Seul Park, Hyoeun Kim, Nuri Yun, Boyoung Joung
Small-interfering RNA (siRNA) therapy is considered a powerful therapeutic strategy for treating cardiac hypertrophy, an important risk factor for subsequent cardiac morbidity and mortality. However, the lack of safe and efficient in vivo delivery of siRNAs is a major challenge for broadening its clinical applications. Small extracellular vesicles (sEVs) are a promising delivery system for siRNAs but have limited cell/tissue-specific targeting ability. In this study, a new generation of heart-targeting sEVs (CEVs) has been developed by conjugating cardiac-targeting peptide (CTP) to human peripheral blood-derived sEVs (PB-EVs), using a simple, rapid and scalable method based on bio-orthogonal copper-free click chemistry...
October 2023: Journal of Extracellular Vesicles
https://read.qxmd.com/read/37793483/bio-clickable-small-extracellular-vesicles-cocktail-therapy-for-ischemic-stroke
#29
JOURNAL ARTICLE
Khan Haroon, Huitong Ruan, Haoran Zheng, Shengju Wu, Ze Liu, Xiaojing Shi, Yaohui Tang, Guo-Yuan Yang, Zhijun Zhang
Delivering large therapeutic molecules via the blood-brain barrier to treat ischemic stroke remains challenging. NR2B9c is a potent neuroprotective peptide but it's safe and targeted delivery to the brain requires an efficient, natural, and non-immunogenic delivery technique. Small extracellular vesicles (sEVs) have shown great potential as a non-immunogenic, natural cargo delivery system; however, tailoring of its inefficient brain targeting is desired. Here, we coupled rabies virus glycoprotein 29 with sEVs surface via bio-orthogonal click chemistry reactions, followed by loading of NR2B9c, ultimately generating stroke-specific therapeutic COCKTAIL (sEVs-COCKTAIL)...
October 2, 2023: Journal of Controlled Release
https://read.qxmd.com/read/37762340/non-canonical-amino-acids-in-analyses-of-protease-structure-and-function
#30
REVIEW
Peter Goettig, Nikolaj G Koch, Nediljko Budisa
All known organisms encode 20 canonical amino acids by base triplets in the genetic code. The cellular translational machinery produces proteins consisting mainly of these amino acids. Several hundred natural amino acids serve important functions in metabolism, as scaffold molecules, and in signal transduction. New side chains are generated mainly by post-translational modifications, while others have altered backbones, such as the β- or γ-amino acids, or they undergo stereochemical inversion, e...
September 13, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37723244/large-stokes-shift-fluorescent-rnas-for-dual-emission-fluorescence-and-bioluminescence-imaging-in-live-cells
#31
JOURNAL ARTICLE
Li Jiang, Xin Xie, Ni Su, Dasheng Zhang, Xianjun Chen, Xiaochen Xu, Bibi Zhang, Kaiyi Huang, Jingwei Yu, Mengyue Fang, Bingkun Bao, Fangting Zuo, Lipeng Yang, Rui Zhang, Huiwen Li, Xinyi Huang, Zhengda Chen, Qingmei Zeng, Renmei Liu, Qiuning Lin, Yuzheng Zhao, Aiming Ren, Linyong Zhu, Yi Yang
Fluorescent RNAs, aptamers that bind and activate small fluorogenic dyes, have provided a particularly attractive approach to visualizing RNAs in live cells. However, the simultaneous imaging of multiple RNAs remains challenging due to a lack of bright and stable fluorescent RNAs with bio-orthogonality and suitable spectral properties. Here, we develop the Clivias, a series of small, monomeric and stable orange-to-red fluorescent RNAs with large Stokes shifts of up to 108 nm, enabling the simple and robust imaging of RNA with minimal perturbation of the target RNA's localization and functionality...
September 18, 2023: Nature Methods
https://read.qxmd.com/read/37716283/imaging-immune-checkpoint-networks-in-cancer-tissues-with-supermultiplexed-sers-nanoprobes
#32
JOURNAL ARTICLE
Jin Li, Fugang Liu, Xinyuan Bi, Jian Ye
Combined immune checkpoint (ICP) inhibitors maximize immune response rates of patients compared to the single-drug treatment strategy in cancer immunotherapy, and prediction of such optimal combinations requires high-throughput imaging techniques and suitable data analysis. In this work, we report a rational strategy for predicting combined drugs of ICP inhibitors based on supermultiplexed surface-enhanced Raman scattering (SERS) imaging and correlation network analysis. To this end, we first built an ultrasensitive and supermultiplexed volume-active SERS (VASERS) nanoprobe platform, where Raman molecules are randomly arranged in 3D volumetric electromagnetic hotspots...
September 12, 2023: Biomaterials
https://read.qxmd.com/read/37698038/ligating-catalytically-active-peptides-onto-microporous-polymers-a-general-route-toward-specifically-functional-high-surface-area-platforms
#33
JOURNAL ARTICLE
Steffen A Busche, Michael Traxler, Arne Thomas, Hans G Börner
A versatile post-synthetic modification strategy to functionalize a high surface area microporous network (MPN-OH) by bioorthogonal inverse electron-demand Diels-Alder (IEDDA) ligation is presented. While the polymer matrix is modified with a readily accessible norbornene isocyanate (Nb-NCO), a set of functional entities, presenting the robust asymmetric 1,2,4,5-tetrazine (Tz) allows easy functionalization of the MPN by chemoselective Nb/Tz ligation. A generic route is demonstrated, modulating the internal interfaces by introducing carboxylates, amides or amino acids as well as an oligopeptide d-Pro-Pro-Glu organocatalyst...
September 12, 2023: ChemSusChem
https://read.qxmd.com/read/37696954/discovery-of-l-threonine-transaldolases-for-enhanced-biosynthesis-of-beta-hydroxylated-amino-acids
#34
JOURNAL ARTICLE
Michaela A Jones, Neil D Butler, Shelby R Anderson, Sean A Wirt, Ishika Govil, Xinyi Lyu, Yinzhi Fang, Aditya M Kunjapur
Beta-hydroxy non-standard amino acids (β-OH-nsAAs) have utility as small molecule drugs, precursors for beta-lactone antibiotics, and building blocks for polypeptides. While the L-threonine transaldolase (TTA), ObiH, is a promising enzyme for β-OH-nsAA biosynthesis, little is known about other natural TTA sequences. We ascertained the specificity of the TTA enzyme class more comprehensively by characterizing 12 candidate TTA gene products across a wide range (20-80%) of sequence identities. We found that addition of a solubility tag substantially enhanced the soluble protein expression level within this difficult-to-express enzyme family...
September 11, 2023: Communications Biology
https://read.qxmd.com/read/37694972/scaffold-free-multicellular-3d-tissue-constructs-utilizing-bio-orthogonal-click-strategy
#35
JOURNAL ARTICLE
Yurui Xu, Anwei Zhou, Weiwei Chen, Xinghai Ning
Multicellular 3D tissue constructs (MTCs) are important in biomedical research due to their capacity to accurately mimic the structure and variation found in real tissues. This study presents a novel bio-orthogonal engineering strategy (BIEN), a transformative scaffold-free approach, to create advanced MTCs. BIEN harnesses the cellular biosynthetic machinery to incorporate bio-orthogonal azide reporters into cell surface glycoconjugates, followed by a click reaction with multiarm PEG, resulting in rapid assembly of MTCs...
September 11, 2023: Nano Letters
https://read.qxmd.com/read/37659815/versatile-click-alginate-hydrogels-with-protease-sensitive-domains-as-cell-responsive-instructive-3d-microenvironments
#36
JOURNAL ARTICLE
Mariana I Neves, Mariana V Magalhães, Sílvia J Bidarra, Lorenzo Moroni, Cristina C Barrias
Alginate (ALG) is a widely used biomaterial to create artificial extracellular matrices (ECM) for tissue engineering. Since it does not degrade in the human body, imparting proteolytic sensitivity to ALG hydrogels leverages their properties as ECM-mimics. Herein, we explored the strain-promoted azide-alkyne cycloaddition (SPAAC) as a biocompatible and bio-orthogonal click-chemistry to graft cyclooctyne-modified alginate (ALG-K) with bi-azide-functionalized PVGLIG peptides. These are sensitive to matrix metalloproteinase (MMP) and may act as crosslinkers...
November 15, 2023: Carbohydrate Polymers
https://read.qxmd.com/read/37655167/the-application-of-bio-orthogonality-for-in-vivo-animal-imaging
#37
REVIEW
Jun Yang, Biyue Zhu, Chongzhao Ran
The application of bio-orthogonality has greatly facilitated numerous aspects of biological studies in recent years. In particular, bio-orthogonal chemistry has transformed biological research, including in vitro conjugate chemistry, target identification, and biomedical imaging. In this review, we highlighted examples of bio-orthogonal in vivo imaging published in recent years. We grouped the references into two major categories: bio-orthogonal chemistry-related imaging and in vivo imaging with bio-orthogonal nonconjugated pairing...
August 28, 2023: Chem Biomed Eng
https://read.qxmd.com/read/37654580/chemical-probe-for-imaging-of-polo-like-kinase-4-and-centrioles
#38
JOURNAL ARTICLE
Aleksandar Salim, Philipp Werther, Georgios N Hatzopoulos, Luc Reymond, Richard Wombacher, Pierre Gönczy, Kai Johnsson
Polo-like kinase (Plk4) is a serine/threonine-protein kinase that is essential for biogenesis of the centriole organelle and is enriched at centrioles. Herein, we introduce Cen-TCO, a chemical probe based on the Plk4 inhibitor centrinone, to image Plk4 and centrioles in live or fixed cultured human cells. Specifically, we established a bio-orthogonal two-step labeling system that enables the Cen-TCO-mediated imaging of Plk4 by STED super-resolution microscopy. Such direct labeling of Plk4 results in an increased resolution in STED imaging compared with using anti-Plk4 antibodies, underlining the importance of direct labeling strategies for super-resolution microscopy...
August 28, 2023: JACS Au
https://read.qxmd.com/read/37637744/gen-click-genetically-encodable-click-reactions-for-spatially-restricted-metabolite-labeling
#39
JOURNAL ARTICLE
Pratyush Kumar Mishra, Nirmali Sharma, Hyunwoo Kim, Changwook Lee, Hyun-Woo Rhee
Chemical reactions for the in situ modification of biomolecules within living cells are under development. Among these reactions, bio-orthogonal reactions such as click chemistry using copper(I) and Staudinger ligation are widely used for specific biomolecule tracking in live systems. However, currently available live cell copper(I)-catalyzed azide/alkyne cycloaddition reactions are not designed in a spatially resolved manner. Therefore, we developed the "GEN-Click" system, which can target the copper(I)-catalyzed azide/alkyne cycloaddition reaction catalysts proximal to the protein of interest and can be genetically expressed in a live cell...
August 23, 2023: ACS Central Science
https://read.qxmd.com/read/37631074/exploring-the-chemical-properties-and-medicinal-applications-of-tetramethylthiocycloheptyne-sulfoximine-used-in-strain-promoted-azide-alkyne-cycloaddition-reactions
#40
JOURNAL ARTICLE
Matt Timmers, Andi Kipper, Raphael Frey, Stef Notermans, Maksym Voievudskyi, Claire Wilson, Nina Hentzen, Michael Ringle, Clara Bovino, Bernhard Stump, Cristianne J F Rijcken, Tina Vermonden, Ingrid Dijkgraaf, Rob Liskamp
The recently developed compound, tetramethylthiocycloheptyne sulfoximine (TMTHSI), has shown to be a promising strained alkyne for strain-promoted azide-alkyne cycloaddition (SPAAC), metal-free click chemistry. This research explores the properties of TMTHSI-based compounds via three aspects: (1) large-scale production, (2) unique stability in acidic conditions and its subsequent use in peptide synthesis, and (3) the functionalization of antibodies. Here, it is shown that (1) scale-up is achieved on a scale of up to 100 g...
August 15, 2023: Pharmaceuticals
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