Cell Chemical Biology最新文献_第10页

Anti-tumor immunotherapy using engineered bacterial outer membrane vesicles fused to lysosome-targeting chimeras mediated by transferrin receptor 利用融合了转铁蛋白受体介导的溶酶体靶向嵌合体的工程细菌外膜囊泡进行抗肿瘤免疫疗法

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.01.002

Ling-Yan Su , Yang Tian , Qiang Zheng , Yu Cao , Mengyu Yao , Shuangping Wang , Wen Xu , Chuyu Xi , Andrea Clocchiatti , Guangjun Nie , Hejiang Zhou

{"title":"Anti-tumor immunotherapy using engineered bacterial outer membrane vesicles fused to lysosome-targeting chimeras mediated by transferrin receptor","authors":"Ling-Yan Su , Yang Tian , Qiang Zheng , Yu Cao , Mengyu Yao , Shuangping Wang , Wen Xu , Chuyu Xi , Andrea Clocchiatti , Guangjun Nie , Hejiang Zhou","doi":"10.1016/j.chembiol.2024.01.002","DOIUrl":"10.1016/j.chembiol.2024.01.002","url":null,"abstract":"<div><p>The lysosome-targeting chimera (LYTAC) approach has shown promise for the targeted degradation of secreted and membrane proteins via lysosomes. However, there have been challenges in design, development, and targeting. Here, we have designed a genetically engineered transferrin receptor (TfR)-mediated lysosome-targeting chimera (TfR-LYTAC) that is efficiently internalized via TfR-mediate endocytosis and targets PD-L1 for lysosomal degradation in cultured cells but not <em>in vivo</em> due to short half-life and poor tumor targeting. A delivery platform was developed by fusing TfR-LYTAC to the surface of bacterial outer membrane vesicles (OMVs). The engineered OMV-LYTAC combines PD-1/PD-L1 pathway inhibition with LYTAC and immune activation by bacterial OMVs. OMV-LYTAC significantly reduced tumor growth <em>in vivo</em>. We have provided a modular and simple genetic strategy for lysosomal degradation as well as a delivery platform for <em>in vivo</em> tumor targeting. The study paves the way for the targeting and degradation of extracellular proteins using the TfR-LYTAC system.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139677098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induced proximity in biology and therapeutics 生物学和治疗学中的诱导接近性

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.05.017

The Cell Chemical Biology editorial team

引用次数: 0

The cyclimids: Degron-inspired cereblon binders for targeted protein degradation 环亚胺：受 Degron 启发的脑龙结合剂，用于靶向降解蛋白质

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.01.003

Saki Ichikawa , N. Connor Payne , Wenqing Xu , Chia-Fu Chang , Nandini Vallavoju , Spencer Frome , Hope A. Flaxman , Ralph Mazitschek , Christina M. Woo

{"title":"The cyclimids: Degron-inspired cereblon binders for targeted protein degradation","authors":"Saki Ichikawa , N. Connor Payne , Wenqing Xu , Chia-Fu Chang , Nandini Vallavoju , Spencer Frome , Hope A. Flaxman , Ralph Mazitschek , Christina M. Woo","doi":"10.1016/j.chembiol.2024.01.003","DOIUrl":"10.1016/j.chembiol.2024.01.003","url":null,"abstract":"<div><p>Cereblon (CRBN) is an E3 ligase substrate adapter widely exploited for targeted protein degradation (TPD) strategies. However, achieving efficient and selective target degradation is a preeminent challenge with ligands that engage CRBN. Here, we report that the cyclimids, ligands derived from the C-terminal cyclic imide degrons of CRBN, exhibit distinct modes of interaction with CRBN and offer a facile approach for developing potent and selective bifunctional degraders. Quantitative TR-FRET-based characterization of 60 cyclimid degraders in binary and ternary complexes across different substrates revealed that ternary complex binding affinities correlated strongly with cellular degradation efficiency. Our studies establish the unique properties of the cyclimids as versatile warheads in TPD and a systematic biochemical approach for quantifying ternary complex formation to predict their cellular degradation activity, which together will accelerate the development of ligands that engage CRBN.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Velcrin compounds activate the SLFN12 tRNase to induce tomoptosis Velcrin 化合物激活 SLFN12 tRNase，诱导细胞凋亡

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.05.012

Heidi Greulich

引用次数: 0

NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers NAMPT靶向药物PROTAC和烟酸联合给药对NAPRT缺陷泛癌具有安全、稳健的抗肿瘤疗效

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.05.007

Xiaotong Zhu , Ye Li , Haixia Liu , Yuetong Wang , Renhong Sun , Zhenzhou Jiang , Chun Hou , Xianyu Hou , Suming Huang , Huijuan Zhang , Haopeng Wang , Biao Jiang , Xiaobao Yang , Bin Xu , Gaofeng Fan

{"title":"NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers","authors":"Xiaotong Zhu , Ye Li , Haixia Liu , Yuetong Wang , Renhong Sun , Zhenzhou Jiang , Chun Hou , Xianyu Hou , Suming Huang , Huijuan Zhang , Haopeng Wang , Biao Jiang , Xiaobao Yang , Bin Xu , Gaofeng Fan","doi":"10.1016/j.chembiol.2024.05.007","DOIUrl":"10.1016/j.chembiol.2024.05.007","url":null,"abstract":"<div><p>Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the biosynthesis of nicotinamide adenine dinucleotide (NAD<sup>+</sup>), making it a potential target for cancer therapy. Two challenges hinder its translation in the clinic: targeting the extracellular form of NAMPT (eNAMPT) remains insufficient, and side effects are observed in normal tissues. We previously utilized proteolysis-targeting chimera (PROTAC) to develop two compounds capable of simultaneously degrading iNAMPT and eNAMPT. Unfortunately, the pharmacokinetic properties were inadequate, and toxicities similar to those associated with traditional inhibitors arose. We have developed a next-generation PROTAC molecule 632005 to address these challenges, demonstrating exceptional target selectivity and bioavailability, improved <em>in vivo</em> exposure, extended half-life, and reduced clearance rate. When combined with nicotinic acid, 632005 exhibits safety and robust efficacy in treating NAPRT-deficient pan-cancers, including xenograft models with hematologic malignancy and prostate cancer and patient-derived xenograft (PDX) models with liver cancer. Our findings provide clinical references for patient selection and treatment strategies involving NAMPT-targeting PROTACs.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Current advances in photocatalytic proximity labeling 光催化近距离标记的最新进展

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.03.012

Steve D. Knutson , Benito F. Buksh , Sean W. Huth , Danielle C. Morgan , David W.C. MacMillan

引用次数: 0

Tools to investigate the cell surface: Proximity as a central concept in glycoRNA biology 研究细胞表面的工具：接近性是糖核糖核酸生物学的核心概念

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.04.015

Lauren Kageler , Jonathan Perr , Ryan A. Flynn

{"title":"Tools to investigate the cell surface: Proximity as a central concept in glycoRNA biology","authors":"Lauren Kageler , Jonathan Perr , Ryan A. Flynn","doi":"10.1016/j.chembiol.2024.04.015","DOIUrl":"10.1016/j.chembiol.2024.04.015","url":null,"abstract":"<div><p>Proximity is a fundamental concept in chemistry and biology, referring to the convergence of molecules to facilitate new molecular interactions or reactions. Hybrid biopolymers like glycosylphosphatidylinositol (GPI)-anchored proteins, ubiquitinated proteins, glycosylated RNAs (glycoRNAs), and RNAylated proteins exemplify this by covalent bonding of moieties that are often orthogonally active. Hybrid molecules like glycoRNAs are localized to new physical spaces, generating new interfaces for biological functions. To fully investigate the compositional and spatial features of molecules like glycoRNAs, flexible genetic and chemical tools that encompass different encoding and targeting biopolymers are required. Here we discuss concepts of molecular proximity and explore newer proximity labeling technologies that facilitate applications in RNA biology, cell surface biology, and the interface therein with a particular focus on glycoRNA biology. We review the advantages and disadvantages of methods pertaining to cell surface RNA identification and provide insights into the vast opportunities for method development in this area.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Get your receptors in a knot with new Wnt signaling agonists 新型 Wnt 信号激动剂让您的感受器打结

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.05.010

Lucie Wolf , Stephane Angers

引用次数: 0

Meet the authors: Lauren Kageler, Jonathan Perr, and Ryan A. Flynn 与作者见面：Lauren Kageler、Jonathan Perr 和 Ryan A. Flynn

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.05.013

Lauren Kageler, Jonathan Perr, Ryan A. Flynn

引用次数: 0

Chemoproteomic profiling of substrate specificity in gut microbiota-associated bile salt hydrolases 肠道微生物相关胆盐水解酶底物特异性的化学蛋白质组学分析

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-17 DOI: 10.1016/j.chembiol.2024.05.009

Lin Han, Augustus Pendleton, Adarsh Singh, Raymond Xu, Samantha A. Scott, Jaymee A. Palma, Peter Diebold, Kien P. Malarney, Ilana L. Brito, Pamela V. Chang

{"title":"Chemoproteomic profiling of substrate specificity in gut microbiota-associated bile salt hydrolases","authors":"Lin Han, Augustus Pendleton, Adarsh Singh, Raymond Xu, Samantha A. Scott, Jaymee A. Palma, Peter Diebold, Kien P. Malarney, Ilana L. Brito, Pamela V. Chang","doi":"10.1016/j.chembiol.2024.05.009","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.05.009","url":null,"abstract":"<p>The gut microbiome possesses numerous biochemical enzymes that biosynthesize metabolites that impact human health. Bile acids comprise a diverse collection of metabolites that have important roles in metabolism and immunity. The gut microbiota-associated enzyme that is responsible for the gateway reaction in bile acid metabolism is bile salt hydrolase (BSH), which controls the host’s overall bile acid pool. Despite the critical role of these enzymes, the ability to profile their activities and substrate preferences remains challenging due to the complexity of the gut microbiota, whose metaproteome includes an immense diversity of protein classes. Using a systems biochemistry approach employing activity-based probes, we have identified gut microbiota-associated BSHs that exhibit distinct substrate preferences, revealing that different microbes contribute to the diversity of the host bile acid pool. We envision that this chemoproteomic approach will reveal how secondary bile acid metabolism controlled by BSHs contributes to the etiology of various inflammatory diseases.</p>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0