共查询到20条相似文献,搜索用时 218 毫秒
1.
Yangyang Xie Xiaotong Li Jingyi Wu Huiling Zeng Hamza Boucetta Binru Wang Pei Yang Wei He 《中国化学快报》2023,34(9):108202-82
Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR) on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment. This new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain, circumventing the restriction of major histocompatibility complex. This review summarized the structure/design of CAR-T cells and the evolution process this technology went through, displaying... 相似文献
2.
Koichi Sasaki Minori Harada Yoshiki Miyashita Hiroshi Tagawa Akihiro Kishimura Takeshi Mori Yoshiki Katayama 《Chemical science》2020,11(12):3208
Redirecting endogenous antibodies in the bloodstream to tumor cells using synthetic molecules is a promising approach to trigger anti-tumor immune responses. However, current molecular designs only enable the use of a small fraction of endogenous antibodies, limiting the therapeutic potential. Here, we report Fc-binding antibody-recruiting molecules (Fc-ARMs) as the first example addressing this issue. Fc-ARMs are composed of an Fc-binding peptide and a targeting ligand, enabling the exploitation of endogenous antibodies through constant affinity to the Fc region of antibodies, whose sequence is conserved in contrast to the Fab region. We show that Fc-ARM targeting folate receptor-α (FR-α) redirects a clinically used antibody mixture to FR-α+ cancer cells, resulting in cancer cell lysis by natural killer cells in vitro. Fc-ARMs successfully interacted with antibodies in vivo and accumulated in tumors. Furthermore, Fc-ARMs recruited antibodies to suppress tumor growth in a mouse model. Thus, Fc-ARMs have the potential to be a novel class of cancer immunotherapeutic agents.Fc-binding antibody-recruiting molecules provide robust and sufficient opportunities to employ endogenous antibodies for anti-tumor immune responses. 相似文献
3.
Tom S. Carter Dr. Tiddo J. Mooibroek Patrick F. N. Stewart Prof. Matthew P. Crump Dr. M. Carmen Galan Prof. Anthony P. Davis 《Angewandte Chemie (International ed. in English)》2016,55(32):9311-9315
Biomimetic carbohydrate receptors (“synthetic lectins”) have potential as agents for biological research and medicine. However, although effective strategies are available for “all‐equatorial” carbohydrates (glucose, etc.), the recognition of other types of saccharide under natural (aqueous) conditions is less well developed. Herein we report a new approach based on a pyrene platform with polar arches extending from aryl substituents. The receptors are compatible with axially substituted carbohydrates, and also feature two identical binding sites, thus mimicking the multivalency observed for natural lectins. A variant with negative charges forms 1:2 host/guest complexes with aminosugars, with K1>3000 m ?1 for axially substituted mannosamine, whereas a positively charged version binds the important α‐sialyl unit with K1≈1300 m ?1. 相似文献
4.
Dongxia Chen Yaying Lin Yifan Fan Lingxuan Li Chenlei Tan Junjie Wang Prof. Hongyu Lin Prof. Jinhao Gao 《Angewandte Chemie (International ed. in English)》2023,62(50):e202313753
The abnormality in the glycosylation of surface proteins is critical for the growth and metastasis of tumors and their capacity for immunosuppression and drug resistance. This anomaly offers an entry point for real-time analysis on glycosylation fluctuations. In this study, we report a strategy, glycan metabolic fluorine labeling (MEFLA), for selectively tagging glycans of tumor cells. As a proof of concept, we synthesized two fluorinated unnatural monosaccharides with distinctive 19F chemical shifts (Ac4ManNTfe and Ac4GalNTfa). These two probes could undergo selective uptake by tumor cells and subsequent incorporation into surface glycans. This approach enables efficient and specific 19F labeling of tumor cells, which permits in vivo tracking of tumor cells and in situ assessment of glycosylation changes by 19F MRI. The efficiency and specificity of our probes for labeling tumor cells were verified in vitro with A549 cells. The feasibility of our method was further validated with in vivo experiments on A549 tumor-bearing mice. Moreover, the capacity of our approach for assessing glycosylation changes of tumor cells was illustrated both in vitro and in vivo. Our studies provide a promising means for visualizing tumor cells in vivo and assessing their glycosylation variations in situ through targeted multiplexed 19F MRI. 相似文献
5.
Callicarpenal (1), a natural terpenoid isolated from American beautyberry (Callicarpa americana), has shown significant repellent activities against mosquitoes, ticks, and imported fire ants. Here we report our efficient synthetic approach to this natural product, and preliminary results of the mosquito biting-deterrent effects of callicarpenal as well as its synthetic precursors and related C8-epimers. The synthetic strategy allows rapid access to various epimers and analogues of the natural product that can be used to explore its structure-activity relationship and optimize its biological properties. 相似文献
6.
《中国化学快报》2021,32(12):3687-3695
Cancer is a serious threat to humans due to its high mortality. The efforts to fully understand cancer and to fight against it have never been stopped. The traditional therapies, such as surgery, radiotherapy and chemotherapy, are useful but cannot meet the increasing demands of patients. As such, novel approaches against cancer are urgently required. It has been found that the acidic tumor microenvironment plays important roles in promoting the cancer progression. In recent years, sodium bicarbonate (NaHCO3), a simple inorganic salt, has been found to be able to reverse the pH of tumor microenvironment and inhibit the invasion, metastasis, immune evasion, drug resistance and hypoxia of tumor cells. Thus, NaHCO3-based therapy is a potential approach for the treatment of cancer, and the related studies have been increasingly reported. Herein, we aim to provide a comprehensive understanding of the acidic tumor microenvironment and summarize the applications and mechanisms of NaHCO3 in cancer therapy. The combination of NaHCO3 with chemotherapy, immunotherapy or nanoparticles systems is discussed. In addition, the concerns of NaHCO3 in clinical use and the potential ways to use NaHCO3 for cancer therapy are also discussed. 相似文献
7.
Dr. Wenyao Zhen Yang Liu Wei Wang Prof. Mengchao Zhang Wenxue Hu Xiaodan Jia Chao Wang Prof. Xiue Jiang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(24):9578-9584
Chaos and the natural evolution of tumor systems can lead to the failure of tumor therapies. Herein, we demonstrate that iridium oxide nanoparticles (IrOx) possess acid-activated oxidase and peroxidase-like functions and wide pH-dependent catalase-like properties. The integration of glucose oxidase (GOD) unlocked the oxidase and peroxidase activities of IrOx by the production of gluconic acid from glucose by GOD catalysis in cancer cells, and the produced H2O2 was converted into O2 to compensate its consumption in GOD catalysis owing to the catalase-like function of the nanozyme, thus resulting in the continual consumption of glucose and the self-supply of substrates to generate superoxide anion and hydroxyl radical. Moreover, IrOx can constantly consume glutathione (GSH) by self-cyclic valence alternation of IrIV and IrIII. These cascade reactions lead to a “butterfly effect” of initial starvation therapy and the subsequent pressure of multiple reactive oxygen species (ROS) to completely break the self-adaption of cancer cells. 相似文献
8.
Liu-Yi Liu Dr. Wenting Liu Dr. Kang-Nan Wang Bo-Chen Zhu Xiao-Yu Xia Prof. Dr. Liang-Nian Ji Prof. Dr. Zong-Wan Mao 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(24):9806-9813
G-quadruplex DNA show structural polymorphism, leading to challenges in the use of selective recognition probes for the accurate detection of G-quadruplexes in vivo. Herein, we present a tripodal cationic fluorescent probe, NBTE , which showed distinguishable fluorescence lifetime responses between G-quadruplexes and other DNA topologies, and fluorescence quantum yield (Φf) enhancement upon G-quadruplex binding. We determined two NBTE -G-quadruplex complex structures with high Φf values by NMR spectroscopy. The structures indicated NBTE interacted with G-quadruplexes using three arms through π–π stacking, differing from that with duplex DNA using two arms, which rationalized the higher Φf values and lifetime response of NBTE upon G-quadruplex binding. Based on photon counts of FLIM, we detected the percentage of G-quadruplex DNA in live cells with NBTE and found G-quadruplex DNA content in cancer cells is 4-fold that in normal cells, suggesting the potential applications of this probe in cancer cell detection. 相似文献
9.
Nicholas Lorig-Roach Frances Hamkins-Indik Tyler A. Johnson Karen Tenney Frederick A. Valeriote Phillip Crews 《Tetrahedron》2018,74(2):217-223
Our quest to isolate and characterize natural products with in vitro solid tumor selectivity is driven by access to repositories of Indo-Pacific sponge extracts. In this project an extract of a species of Haplosclerida sponge obtained from the US NCI Natural Products Repository displayed, by in vitro disk diffusion assay (DDA) and IC50 determinations, selective cytotoxicity with modest potency to a human pancreatic cancer cell line (PANC-1) relative to the human lymphoblast leukemia cell line (CCRF-CEM). Two brominated indoles, the known 6-bromo conicamin (1) and the new derivative, 6-Br-8-keto-conicamin A (2), were identified and 2 (IC50 1.5 μM for the natural product vs 4.1 μM for the synthetic material) was determined to be responsible for the cytotoxic activity of the extract against the PANC-1 tumor cell line. The new natural product and ten additional analogs were prepared for further SAR testing. 相似文献
10.
Chad Plumet Achmet Said Mohamed Tanguy Vendeuvre Brigitte Renoux Jonathan Clarhaut Sbastien Papot 《Chemical science》2021,12(26):9017
Metabolic glycoengineering with unnatural sugars became a valuable tool for introducing recognition markers on the cell membranes via bioorthogonal chemistry. By using this strategy, we functionalized the surface of tumor and T cells using complementary artificial markers based on both β-cyclodextrins (β-CDs) and adamantyl trimers, respectively. Once tied on cell surfaces, the artificial markers induced cell–cell adhesion through non-covalent click chemistry. These unnatural interactions between A459 lung tumor cells and Jurkat T cells triggered the activation of natural killer (NK) cells thanks to the increased production of interleukin-2 (IL-2) in the vicinity of cancer cells, leading ultimately to their cytolysis. The ready-to-use surface markers designed in this study can be easily inserted on the membrane of a wide range of cells previously submitted to metabolic glycoengineering, thereby offering a simple way to investigate and manipulate intercellular interactions.We designed complementary artificial markers that were introduced on the surface of cells previously modified by metabolic glycoengineering. These recognition markers enable unnatural cell–cell adhesion through non-covalent click chemistry. 相似文献
11.
Pui Kei Mou Eun Ju Yang Changxiang Shi Guowen Ren Shishi Tao Joong Sup Shim 《Experimental & molecular medicine》2021,53(5):835
Recent advances in high-throughput sequencing technologies and data science have facilitated the development of precision medicine to treat cancer patients. Synthetic lethality is one of the core methodologies employed in precision cancer medicine. Synthetic lethality describes the phenomenon of the interplay between two genes in which deficiency of a single gene does not abolish cell viability but combined deficiency of two genes leads to cell death. In cancer treatment, synthetic lethality is leveraged to exploit the dependency of cancer cells on a pathway that is essential for cell survival when a tumor suppressor is mutated. This approach enables pharmacological targeting of mutant tumor suppressors that are theoretically undruggable. Successful clinical introduction of BRCA-PARP synthetic lethality in cancer treatment led to additional discoveries of novel synthetic lethal partners of other tumor suppressors, including p53, PTEN, and RB1, using high-throughput screening. Recent work has highlighted aurora kinase A (AURKA) as a synthetic lethal partner of multiple tumor suppressors. AURKA is a serine/threonine kinase involved in a number of central biological processes, such as the G2/M transition, mitotic spindle assembly, and DNA replication. This review introduces synthetic lethal interactions between AURKA and its tumor suppressor partners and discusses the potential of AURKA inhibitors in precision cancer medicine.Subject terms: Targeted therapies, Drug discovery 相似文献
12.
Tumor differentiation is a therapeutic strategy aimed at reactivating the endogenous differentiation program of cancer cells and inducing cancer cells to mature and differentiate into other types of cells. It has been found that a variety of natural small-molecule drugs can induce tumor cell differentiation both in vitro and in vivo. Relevant molecules involved in the differentiation process may be potential therapeutic targets for tumor cells. Compared with synthetic drugs, natural small-molecule antitumor compounds have the characteristics of wide sources, structural diversity and low toxicity. In addition, natural drugs with structural modification and transformation have relatively concentrated targets and enhanced efficacy. Therefore, using natural small-molecule compounds to induce malignant cell differentiation represents a more targeted and potential low-toxicity means of tumor treatment. In this review, we focus on natural small-molecule compounds that induce differentiation of myeloid leukemia cells, osteoblasts and other malignant cells into functional cells by regulating signaling pathways and the expression of specific genes. We provide a reference for the subsequent development of natural small molecules for antitumor applications and promote the development of differentiation therapy. 相似文献
13.
Wenyao Zhen Yang Liu Wei Wang Mengchao Zhang Wenxue Hu Xiaodan Jia Chao Wang Xiue Jiang 《Angewandte Chemie (International ed. in English)》2020,59(24):9491-9497
Chaos and the natural evolution of tumor systems can lead to the failure of tumor therapies. Herein, we demonstrate that iridium oxide nanoparticles (IrOx) possess acid‐activated oxidase and peroxidase‐like functions and wide pH‐dependent catalase‐like properties. The integration of glucose oxidase (GOD) unlocked the oxidase and peroxidase activities of IrOx by the production of gluconic acid from glucose by GOD catalysis in cancer cells, and the produced H2O2 was converted into O2 to compensate its consumption in GOD catalysis owing to the catalase‐like function of the nanozyme, thus resulting in the continual consumption of glucose and the self‐supply of substrates to generate superoxide anion and hydroxyl radical. Moreover, IrOx can constantly consume glutathione (GSH) by self‐cyclic valence alternation of IrIV and IrIII. These cascade reactions lead to a “butterfly effect” of initial starvation therapy and the subsequent pressure of multiple reactive oxygen species (ROS) to completely break the self‐adaption of cancer cells. 相似文献
14.
Targeted Ultrasound‐Assisted Cancer‐Selective Chemical Labeling and Subsequent Cancer Imaging using Click Chemistry
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Hua Wang Marianne Gauthier Jamie R. Kelly Rita J. Miller Ming Xu Prof. Dr. William D. O'Brien Jr. Prof. Dr. Jianjun Cheng 《Angewandte Chemie (International ed. in English)》2016,55(18):5452-5456
Metabolic sugar labeling followed by the use of reagent‐free click chemistry is an established technique for in vitro cell targeting. However, selective metabolic labeling of the target tissues in vivo remains a challenge to overcome, which has prohibited the use of this technique for targeted in vivo applications. Herein, we report the use of targeted ultrasound pulses to induce the release of tetraacetyl N‐azidoacetylmannosamine (Ac4ManAz) from microbubbles (MBs) and its metabolic expression in the cancer area. Ac4ManAz‐loaded MBs showed great stability under physiological conditions, but rapidly collapsed in the presence of tumor‐localized ultrasound pulses. The released Ac4ManAz from MBs was able to label 4T1 tumor cells with azido groups and significantly improved the tumor accumulation of dibenzocyclooctyne (DBCO)‐Cy5 by subsequent click chemistry. We demonstrated for the first time that Ac4ManAz‐loaded MBs coupled with the use of targeted ultrasound could be a simple but powerful tool for in vivo cancer‐selective labeling and targeted cancer therapies. 相似文献
15.
Zdeněk Kejík Tomáš Bříza Jarmila Králová Pavel Martásek Vladimír Král 《Analytical and bioanalytical chemistry》2010,398(5):1865-1870
It is well known that saccharides and their glycoconjugates can have an important influence on various serious pathologic
stages such as cancer. They can regulate tumor proliferation, invasion, hematogenous metastasis, and angiogenesis. These facts
clearly show the importance of cancer saccharide recognition. In medicine, sensor analysis is one of the best methods for
recognition and determination of biologically important analytes. The development and study of sensors for saccharide tumor
markers can open a new way for their detection. Therefore, this review is focused on recognition of saccharide-based cancer
markers by natural or synthetic selective ligands working as bio- and chemosensors. The design and application of these ligands
for cancer diagnosis is a useful direction of research. Moreover, it also opens the possibility of using these agents for
the targeted drug transport required for advanced anticancer therapy. 相似文献
16.
Liu‐Yi Liu Wenting Liu Kang‐Nan Wang Bo‐Chen Zhu Xiao‐Yu Xia Liang‐Nian Ji Zong‐Wan Mao 《Angewandte Chemie (International ed. in English)》2020,59(24):9719-9726
G‐quadruplex DNA show structural polymorphism, leading to challenges in the use of selective recognition probes for the accurate detection of G‐quadruplexes in vivo. Herein, we present a tripodal cationic fluorescent probe, NBTE , which showed distinguishable fluorescence lifetime responses between G‐quadruplexes and other DNA topologies, and fluorescence quantum yield (Φf) enhancement upon G‐quadruplex binding. We determined two NBTE ‐G‐quadruplex complex structures with high Φf values by NMR spectroscopy. The structures indicated NBTE interacted with G‐quadruplexes using three arms through π–π stacking, differing from that with duplex DNA using two arms, which rationalized the higher Φf values and lifetime response of NBTE upon G‐quadruplex binding. Based on photon counts of FLIM, we detected the percentage of G‐quadruplex DNA in live cells with NBTE and found G‐quadruplex DNA content in cancer cells is 4‐fold that in normal cells, suggesting the potential applications of this probe in cancer cell detection. 相似文献
17.
Prof. Dmitry Dar'in Dr. Grigory Kantin Dr. Evgeny Chupakhin Dr. Vladimir Sharoyko Prof. Mikhail Krasavin 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(31):8221-8227
α-Diazo homophotalimides were reacted with various propiolic acids on Rh2(esp)2 catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δα,β-spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural-like Δα,β-spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δα,β-spirobutenolides thus obtained were shown to inhibit thioredoxin reductase, a selenocysteine enzyme target for cancer. Moreover, for the best compound in the series (TrxR IC50 1.49±0.08 μM), by using MALDI-TOF mass-spectrometry it was shown that it selectively binds selenocysteine in the presence of a 10-fold excess of cysteine. This validates the new compound as a promising lead for anticancer therapy development. 相似文献
18.
Total synthesis of the originally proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide, has been accomplished by using a [(4+1)+3+3]-peptide fragment-coupling strategy and careful examination and optimization of the multiple dense N-methylated amide-bond formations. The synthetic sample of the proposed coibamide A could not match the natural product in both 1H and 13C NMR spectra, but was found to exhibit low micromolar cytotoxicity against the proliferation of three tested cancer cells. 相似文献
19.
Dorra Aissaoui-Zid Mohamed-Chiheb Saada Wassim Moslah Marie Potier-Cartereau Aude Lemettre Houcemeddine Othman Marc Gaysinski Zaineb Abdelkafi-Koubaa Soumaya Souid Naziha Marrakchi Christophe Vandier Khadija Essafi-Benkhadir Najet Srairi-Abid 《Molecules (Basel, Switzerland)》2021,26(24)
Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC50 of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer. 相似文献
20.
Cai H Huang ZH Shi L Zhao YF Kunz H Li YM 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(23):6396-6406
The membrane‐bound tumor‐associated glycoprotein MUC1 is aberrantly glycosylated in cancer cells compared with normal cells, and is therefore considered an attractive target for cancer immunotherapy. However, tumor‐associated glycopeptides from MUC1 do not elicit a sufficiently robust immune response. Therefore, antitumor vaccines were developed, which consist of MUC1 glycopeptides as the B epitopes and immune‐stimulating toll‐like receptor 2 (TLR 2) lipopeptide ligands. These fully synthetic vaccine candidates were prepared by solid‐phase synthesis of the MUC1 glycopeptides. The Pam3Cys lipopeptide, also synthesized on solid‐phase, was C‐terminally coupled to oligovalent lysine cores, which N‐terminally incorporate O‐propargyl oligoethylene glycol acyl side chains. The MUC1 glycopeptides and lipopeptide lysine constructs were then conjugated by click chemistry to give oligovalent synthetic vaccines. Oligovalent glycopeptide–lipopeptide conjugates are considered more immunogenic than their monovalent analogues. 相似文献