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Evading resistance at the double 躲避双重阻力
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-30 DOI: 10.1038/s41589-024-01772-5
Mohamed I. Barmada, Graeme L. Conn
{"title":"Evading resistance at the double","authors":"Mohamed I. Barmada, Graeme L. Conn","doi":"10.1038/s41589-024-01772-5","DOIUrl":"https://doi.org/10.1038/s41589-024-01772-5","url":null,"abstract":"Synthesis and characterization of new macrolones — fusions of two antibiotic classes with distinct bacterial targets — reveal the basis for their activity and potential design principles that may help combat development of antimicrobial resistance.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"10 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536917","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
Protein Degradation in Focus 聚焦蛋白质降解
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-29 DOI: 10.1038/s41589-024-01757-4
David Zollman, Kirsten McAulay
{"title":"Protein Degradation in Focus","authors":"David Zollman, Kirsten McAulay","doi":"10.1038/s41589-024-01757-4","DOIUrl":"https://doi.org/10.1038/s41589-024-01757-4","url":null,"abstract":"In May 2024, ‘Protein Degradation in Focus’, a special symposium aimed at bringing together scientists in the targeted protein degradation (TPD) field, was held in Dundee, UK. David Zollman and Kirsten McAulay report on the topics discussed and the exciting outlook for science in the TPD space.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"2 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520057","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
Genes and crystals are not so separate 基因与晶体并非截然分开
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-28 DOI: 10.1038/s41589-024-01765-4
Peter G. Vekilov
{"title":"Genes and crystals are not so separate","authors":"Peter G. Vekilov","doi":"10.1038/s41589-024-01765-4","DOIUrl":"https://doi.org/10.1038/s41589-024-01765-4","url":null,"abstract":"The mechanism underlying the formation of crystals in cells is not completely understood. An article now reports on the biochemical control of the crystal genesis in iridophores.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"2 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519270","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
Selective bioorthogonal probe for N-glycan hybrid structures 针对 N-聚糖杂交结构的选择性生物正交探针
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-28 DOI: 10.1038/s41589-024-01756-5
Mana Mohan Mukherjee, Devin Biesbrock, Lara K. Abramowitz, Matteo Pavan, Bhoj Kumar, Peter J. Walter, Parastoo Azadi, Kenneth A. Jacobson, John A. Hanover
{"title":"Selective bioorthogonal probe for N-glycan hybrid structures","authors":"Mana Mohan Mukherjee, Devin Biesbrock, Lara K. Abramowitz, Matteo Pavan, Bhoj Kumar, Peter J. Walter, Parastoo Azadi, Kenneth A. Jacobson, John A. Hanover","doi":"10.1038/s41589-024-01756-5","DOIUrl":"https://doi.org/10.1038/s41589-024-01756-5","url":null,"abstract":"<p>Metabolic incorporation of chemically tagged monosaccharides is a facile means of tagging cellular glycoproteins and glycolipids. However, since the monosaccharide precursors are often shared by several pathways, selectivity has been difficult to attain. For example, <i>N</i>-linked glycosylation is a chemically complex and ubiquitous posttranslational modification, with three distinct classes of GlcNAc-containing <i>N</i>-glycan structures: oligomannose, hybrid and complex. Here we describe the synthesis of 1,3-Pr<sub>2</sub>-6-OTs GlcNAlk (MM-JH-1) as a next-generation metabolic chemical reporter for the selective labeling of hybrid <i>N</i>-glycan structures. We first developed a general strategy for defining the selectivity of labeling with chemically tagged monosaccharides. We then applied this approach to establish that MM-JH-1 is selectively incorporated into hybrid <i>N</i>-glycans. Using this metabolic chemical reporter as a detection tool, we performed imaging and fractionation to define features of the intracellular localization and trafficking of target proteins bearing hybrid <i>N</i>-glycan structures.</p><figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"23 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519271","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
Cracking the diversity of sweet drugs 破解甜味药物的多样性
IF 12.9 1区 生物学
Nature chemical biology Pub Date : 2024-10-24 DOI: 10.1038/s41589-024-01755-6
Sharon Yehuda, Vered Padler-Karavani
{"title":"Cracking the diversity of sweet drugs","authors":"Sharon Yehuda,&nbsp;Vered Padler-Karavani","doi":"10.1038/s41589-024-01755-6","DOIUrl":"10.1038/s41589-024-01755-6","url":null,"abstract":"Characterization of the heterogeneity in the glycosylation of biotherapeutics is crucial for drug development but challenging. Now, an approach allows the rapid analysis of the glycosylation of intact glycoproteins, without prior processing or separation, enabling the study of glycan composition and quality assessment of any glycoprotein drug.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 11","pages":"1397-1398"},"PeriodicalIF":12.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488353","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
Stressing out with electrophiles 用亲电体释放压力
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-24 DOI: 10.1038/s41589-024-01749-4
Caroline Stanton, Kayla Nutsch, Michael J. Bollong
{"title":"Stressing out with electrophiles","authors":"Caroline Stanton, Kayla Nutsch, Michael J. Bollong","doi":"10.1038/s41589-024-01749-4","DOIUrl":"https://doi.org/10.1038/s41589-024-01749-4","url":null,"abstract":"Covalent modification of cysteine by electrophilic small molecules enables broad targeting of the unliganded proteome. A study reveals that cysteine reactive electrophiles can induce widespread degradation of host proteins and remodeling of cellular proteostasis at commonly used concentrations.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"14 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488385","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
Delineating cysteine-reactive compound modulation of cellular proteostasis processes 阐明半胱氨酸反应化合物对细胞蛋白稳态过程的调节作用
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-24 DOI: 10.1038/s41589-024-01760-9
Ashley R. Julio, Flowreen Shikwana, Cindy Truong, Nikolas R. Burton, Emil R. Dominguez, Alexandra C. Turmon, Jian Cao, Keriann M. Backus
{"title":"Delineating cysteine-reactive compound modulation of cellular proteostasis processes","authors":"Ashley R. Julio, Flowreen Shikwana, Cindy Truong, Nikolas R. Burton, Emil R. Dominguez, Alexandra C. Turmon, Jian Cao, Keriann M. Backus","doi":"10.1038/s41589-024-01760-9","DOIUrl":"https://doi.org/10.1038/s41589-024-01760-9","url":null,"abstract":"<p>Covalent modulators and covalent degrader molecules have emerged as drug modalities with tremendous therapeutic potential. Toward realizing this potential, mass spectrometry-based chemoproteomic screens have generated proteome-wide maps of potential druggable cysteine residues. However, beyond these direct cysteine-target maps, the full scope of direct and indirect activities of these molecules on cellular processes and how such activities contribute to reported modes of action, such as degrader activity, remains to be fully understood. Using chemoproteomics, we identified a cysteine-reactive small molecule degrader of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nonstructural protein 14 (nsp14), which effects degradation through direct modification of cysteines in both nsp14 and in host protein disulfide isomerases. This degrader activity was further potentiated by generalized electrophile-induced global protein ubiquitylation, proteasome activation and widespread aggregation and depletion of host proteins, including the formation of stress granules. Collectively, we delineate the wide-ranging impacts of cysteine-reactive electrophilic compounds on cellular proteostasis processes.</p><figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"64 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488354","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
In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides 非生物寡糖对人体肠道乳酸杆菌适应性的体内操纵
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-23 DOI: 10.1038/s41589-024-01763-6
Darryl A. Wesener, Zachary W. Beller, Megan F. Hill, Han Yuan, David B. Belanger, Cheryl Frankfater, Nicolas Terrapon, Bernard Henrissat, Dmitry A. Rodionov, Semen A. Leyn, Andrei Osterman, Johan E. T. van Hylckama Vlieg, Jeffrey I. Gordon
{"title":"In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides","authors":"Darryl A. Wesener, Zachary W. Beller, Megan F. Hill, Han Yuan, David B. Belanger, Cheryl Frankfater, Nicolas Terrapon, Bernard Henrissat, Dmitry A. Rodionov, Semen A. Leyn, Andrei Osterman, Johan E. T. van Hylckama Vlieg, Jeffrey I. Gordon","doi":"10.1038/s41589-024-01763-6","DOIUrl":"https://doi.org/10.1038/s41589-024-01763-6","url":null,"abstract":"<p>Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic <i>Bacteroides</i> in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 <i>Bacteroides</i> strains increased, most prominently <i>B. intestinalis</i>. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate utilization machinery, using retrievable microscopic paramagnetic particles with bound SG oligosaccharides and assaying SG degradation by individual purified <i>B. intestinalis</i> glycoside hydrolases. The results reveal that SGs can selectively co-opt carbohydrate utilization machinery in different human gut <i>Bacteroides</i> and demonstrate a means for identifying artificial carbohydrate structures for targeted bacterial manipulation.</p><figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"31 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487111","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
Bridging the gap in protein targeting 缩小蛋白质靶向的差距
IF 12.9 1区 生物学
Nature chemical biology Pub Date : 2024-10-22 DOI: 10.1038/s41589-024-01766-3
Irene Serrano
{"title":"Bridging the gap in protein targeting","authors":"Irene Serrano","doi":"10.1038/s41589-024-01766-3","DOIUrl":"10.1038/s41589-024-01766-3","url":null,"abstract":"","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 11","pages":"1387-1387"},"PeriodicalIF":12.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452518","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
Targeting proteins to lysosomes with a chemical inducer of arginine methylation 用精氨酸甲基化化学诱导剂将蛋白质定向到溶酶体
IF 14.8 1区 生物学
Nature chemical biology Pub Date : 2024-10-22 DOI: 10.1038/s41589-024-01744-9
{"title":"Targeting proteins to lysosomes with a chemical inducer of arginine methylation","authors":"","doi":"10.1038/s41589-024-01744-9","DOIUrl":"https://doi.org/10.1038/s41589-024-01744-9","url":null,"abstract":"Arginine methylation acts as a signal for intracellular proteins to be degraded in lysosomes. We developed methylarginine targeting chimera (MrTAC), a chemical tool that induces proximity with protein arginine N-methyltransferase 1 (PRMT1) to trigger arginine methylation and thus targeted protein degradation in lysosomes.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"12 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452655","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
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