ACS Bio & Med Chem Au最新文献

{"title":"Glycosylated N-Acyl Phosphoethanolamines as Bacterial Food-Dependent Signaling Molecules in Caenorhabditis Nematodes","authors":"Siva Bandi,&nbsp;Marie-Désirée Schlemper-Scheidt,&nbsp;Rocío Rivera Sánchez,&nbsp;Sylvain Sutour,&nbsp;Gaétan Glauser,&nbsp;Yojiro Ishida and Stephan H. von Reuß*,&nbsp;","doi":"10.1021/acsbiomedchemau.5c00012","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00012","url":null,"abstract":"<p ><i>N</i>-acyl ethanolamines represent conserved lipophilic signaling molecules that function as endogenous ligands at G-protein-coupled receptors, ion channels, and nuclear receptors. Using a combination of comparative ultrahigh-performance liquid chromatography electrospray ionization high-resolution tandem mass spectrometry (UHPLC-ESI-HR-MS^E) analysis and microreactions, a diversity of glycosylated <i>N</i>-acyl phosphoethanolamines were characterized in <i>Caenorhabditis</i> nematodes. Representative examples were enriched by RP-C18 chromatography and identified by NMR spectroscopy. Comparative metabolomics and isotope incorporation experiments revealed that the biosynthesis of the homologous <i>N</i>-acyl building blocks (approximately 50 compounds) depends on the bacterial food source, chain elongation and desaturation of food-derived fatty acids, or their de novo biosynthesis by the nematode, whereas the biosynthesis of medium-chain <i>N</i>-acyl units depends on the peroxisomal β-oxidation cycle via the 3-ketoacyl-<i>S</i>-CoA thiolase <i>daf-22</i>. Glycosylation of these lipophilic <i>N</i>-acyl ethanolamines results in amphiphilic modular metabolites (approximately 100 identified compounds) that are released into the environment and exhibit potential signaling functions. Exclusively male-produced β-sophorosyl <i>N-</i>acyl-phosphoethanolamines like SNAP-13:1cyclo retain females of <i>Caenorhabditis wallacei</i> and <i>Caenorhabditis brenneri</i>, and its biosynthesis requires bacterial cyclo fatty acids 17:1cyclo and 19:1cyclo, thereby translating growth phase-dependent bacterial lipogeneses into a behavioral signal. Amphiphilic 2-(β-glucosyl)-glyceryl <i>N</i>-eicosapentaenoyl phosphoethanolamine (GGp-NAE-20:5), a dominating component of the <i>Caenorhabditis elegans</i> metabolome, represents a water-soluble derivative of <i>N</i>-eicosapentaenoyl ethanolamine (NAE 20:5), potentially enabling intra- and interspecies endocannabinoid signaling.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"602–619"},"PeriodicalIF":4.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of YTHDF2 Ligands by Fragment-Based Design","authors":"Annalisa Invernizzi,&nbsp;Francesco Nai,&nbsp;Rajiv Kumar Bedi,&nbsp;Pablo Andrés Vargas-Rosales,&nbsp;Yaozong Li,&nbsp;Elena Bochenkova,&nbsp;Marcin Herok,&nbsp;František Zálešák and Amedeo Caflisch*,&nbsp;","doi":"10.1021/acsbiomedchemau.5c00099","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00099","url":null,"abstract":"<p ><i>N</i>⁶-Adenosine methylation is the most abundant modification of mRNA. The three members of the YTH domain family proteins (YTHDF1–3) recognize in the cytoplasm the m⁶A-RNA modification. We screened a library of about 500,000 fragments (i.e., molecules with 11–20 non-hydrogen atoms) by docking into YTHDF2, which resulted in the identification of six active compounds among 47 tested in vitro (hit rate of 13%). The acquisition of 28 analogues of the docking hits provided an additional set of 10 active compounds (IC₅₀ &lt; 100 μM). Protein crystallography-guided optimization of a ligand-efficient fragment by the synthesis of 32 derivatives culminated in a series of YTHDF2 ligands, which show low-micromolar affinity measured by a fluorescence polarization (FP) assay and a homogeneous time-resolved fluorescence-based (HTRF) assay. The series is characterized by very favorable ligand efficiency (of about 0.3–0.4 kcal/mol per non-hydrogen atom). Compound <b>23</b> binds to YTHDF2 according to the FP and HTRF assays with a <i>K</i>_d value of 1.3 μM and an IC₅₀ value of 11 μM, respectively, and it is selective against all of the other YTH reader proteins. Several compounds of the series bind to the three YTHDF proteins with similar low-micromolar affinity, while they are less potent for YTHDC1 and YTHDC2. In contrast, compounds <b>17</b> and <b>30</b> bind also to YTHDC2, with <i>K</i>_d of 6.3 and 4.9 μM, respectively. We also disclose six crystal structures of YTHDF2 in the complex with the fragments identified by docking.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"753–765"},"PeriodicalIF":4.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morpholinoethoxy-Substituted Cationic Metal-Free and Metallo Phthalocyanines: In Vitro Photodynamic Therapy Activities, PDT-Induced ROS Level Measurements, and Cellular Death Mechanism","authors":"Muge Serhatli*,&nbsp;Seyma Isik,&nbsp;Ayfer Kalkan,&nbsp;Mukaddes Özçeşmeci,&nbsp;Esin Hamuryudan and Özge Can*,&nbsp;","doi":"10.1021/acsbiomedchemau.5c00137","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00137","url":null,"abstract":"<p >In this study, morpholinoethoxy-attached cationic tetra-substituted phthalocyanines (Pcs), including metal-free (<b>HQH</b>_<b>2</b><b>Pc</b>), zinc (<b>HQZnPc</b>), and indium (<b>HQInPc</b>) derivatives, were synthesized following established protocols. Their structures were confirmed by using standard spectroscopic techniques. The photodynamic therapy (PDT) efficacy of these compounds was evaluated against head, neck, and colon cancer cell lines. Reactive oxygen species (ROS) levels induced by PDT with cationic Pcs were quantified by using dichlorodihydrofluorescein diacetate. To elucidate the mechanisms of action, ROS generation was assessed at two distinct time points: 30 min (immediate response) and 24 h (delayed response) post-PDT. The cellular death mechanisms induced by Pc-mediated PDT in cancer cell lines were investigated using fluorescence staining with Apopxin Green, CytoCalcein Violet 450, and 7-AAD to differentiate apoptotic and necrotic pathways and provide insights into the mode of cell death. The results indicated that the Pcs exhibited minimal cytotoxicity in the absence of light, confirming their safety as photosensitizers. Cationic Pcs, particularly <b>HQZnPc</b>, showed high PDT-induced cytotoxicity and ROS production, primarily inducing apoptosis in cancer cell lines, with FaDu cells exhibiting the highest sensitivity. These results highlight <b>HQZnPc</b>’s strong potential for cancer therapy and underscore the need for further research into its delivery and mechanisms in complex tumor models.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"766–777"},"PeriodicalIF":4.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Jyotshana Saroj,&nbsp;Rahul Dev Verma,&nbsp;Sariyah Akhtar,&nbsp;Neeraj Kumar Verma,&nbsp;Arvind Gupta,&nbsp;Arsh Tripathi,&nbsp;Juhi Sharma,&nbsp;Kalyan Mitra,&nbsp;Mohammad Imran Siddiqi and Jimut Kanti Ghosh*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 3","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Jamie J. Arnold*,&nbsp;Alexandre Martinez,&nbsp;Abha Jain,&nbsp;Xinran Liu,&nbsp;Ibrahim M. Moustafa and Craig E. Cameron*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 3","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144355183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 3","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/bgv005i003_1948123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Syam Sundar Neti,&nbsp;Bo Wang*,&nbsp;Jiayuan Cui,&nbsp;David F. Iwig,&nbsp;Nicholas J. York,&nbsp;Anthony J. Blaszczyk,&nbsp;Matthew R. Bauerle and Squire J. Booker*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 3","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 3","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/bgv005i003_1948124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144355176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Alexander J. Hughes,&nbsp;Julie A. Talbert and Steven D. Townsend*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 3","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Hans-Jörg Schneider*,&nbsp;","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 3","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":3.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144429473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}