ACS Bio & Med Chem Au最新文献

{"title":"Bridging Health Disparity Gaps in Alzheimer’s Disease among Marginalized Populations: Clinical Proteomics as a Case Study","authors":"Henry A. Adeola,&nbsp; and ,&nbsp;Renã A. S. Robinson*,&nbsp;","doi":"10.1021/acsbiomedchemau.5c00074","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00074","url":null,"abstract":"<p >Alzheimer’s disease (AD) and AD-related dementias (ADRD) represent a significant health challenge, with a growing impact on marginalized populations who often experience inequities in overall healthcare access and outcomes. Many factors contribute to these inequalities and can impact the benefits of broad appreciation of new technologies in AD/ADRD to these populations. For example, clinical proteomics offers a promising avenue for early and timely detection of disease and elucidation of the mechanisms of AD/ADRD. Unfortunately, gaps exist in the access and application of proteomic innovations for the health of marginalized communities. This editorial (1) highlights systemic barriers and explores the underlying factors that contribute to these inequities, (2) examines health disparities in the implementation of clinical proteomics tools for the management of AD/ADRD among marginalized populations, and (3) offers opportunities for advancing clinical proteomics in AD/ADRD. Implementation by basic and clinical researchers will lead to a more effective and inclusive approach to combatting AD/ADRD disparities.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"505–518"},"PeriodicalIF":4.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863167","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":"Overcoming Global Antifungal Challenges: Medical and Agricultural Aspects","authors":"László Galgóczy*,&nbsp;","doi":"10.1021/acsbiomedchemau.5c00103","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00103","url":null,"abstract":"<p >The prevalence of fungal infections and contamination has increased alarmingly over the past decade, posing a significant threat to human health and the food supply and negatively affecting welfare. This escalating concern is primarily attributed to the lack of safe, effective, and widely available antifungal agents; the increasing spread of (multi)drug resistance to conventional antifungal treatments; and substantial epidemiological shifts in fungal pathogens. Decision-making bodies have recognized the urgency of this situation and prioritized efforts to address and mitigate the spread of drug-resistant fungal infections by developing and implementing innovative antifungal strategies, including using drug combinations, designing fundamentally new antifungal compounds with fungus-specific mechanisms of action and a minimal risk of resistance development, drug repurposing, and exploring alternative approaches, such as biomolecules, nanotechnology, and biological control. This review aims to provide a comprehensive overview of the current challenges associated with fungal infections in medicine and agriculture as well as the latest advancements and potential solutions.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"531–552"},"PeriodicalIF":4.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863059","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":"A Potent Inhibitor of Caspase-8 Based on the IL-18 Tetrapeptide Sequence Reveals Shared Specificities between Inflammatory and Apoptotic Initiator Caspases","authors":"Christopher M. Bourne,&nbsp;Nicole R. Raniszewski,&nbsp;Ashutosh B. Mahale,&nbsp;Madhura Kulkarni,&nbsp;Patrick M. Exconde,&nbsp;Sherry Liu,&nbsp;Winslow Yost,&nbsp;Tristan J. Wrong,&nbsp;Robert C. Patio,&nbsp;Matilda Kardhashi,&nbsp;Teni Shosanya,&nbsp;Mirai Kambayashi,&nbsp;Bohdana M. Discher,&nbsp;Igor E. Brodsky,&nbsp;George M. Burslem* and Cornelius Y. Taabazuing*,&nbsp;","doi":"10.1021/acsbiomedchemau.4c00146","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.4c00146","url":null,"abstract":"<p >Caspases are a family of cysteine proteases that act as molecular scissors to cleave substrates and regulate biological processes, such as programmed cell death and inflammation. Extensive efforts have been made to identify caspase substrates and to determine the factors that dictate specificity. We recently discovered that human inflammatory caspases (caspases-1, -4, and -5) cleave the cytokines IL-1β and IL-18 in a sequence-dependent manner. Here, we report the development of a new peptide-based probe and inhibitor derived from the tetrapeptide sequence of IL-18 (LESD). The LESD-based inhibitor showed a strong preference for caspase-8 with an IC₅₀ of 50 nM, and was more potent <i>in vitro</i> than the commonly used zIETD-FMK inhibitor, which is considered the most selective and potent caspase-8 inhibitor. We further demonstrated that the LESD-based inhibitor prevents caspase-8 activation during <i>Yersinia pseudotuberculosis</i> infection in primary bone marrow-derived macrophages. In addition, we systematically characterized the selectivity and potency of known substrates and inhibitors of the apoptotic and inflammatory caspases using standardized activity units of each caspase. Our findings reveal that VX-765, a known inhibitor of caspases-1 and -4, also inhibits caspase-8 (IC₅₀ = 1 μM). Even when specificities are shared, the caspases exhibit different efficiencies and potencies for shared substrates and inhibitors. Altogether, we report the development of new tools that will facilitate the study of caspases and their roles in biology.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"565–581"},"PeriodicalIF":4.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863060","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":"ACS Bio & Med Chem Au Recognizes Juneteenth 2025","authors":"Squire J. Booker,&nbsp; and ,&nbsp;Tamra C. Blue-Lahom,&nbsp;","doi":"10.1021/acsbiomedchemau.5c00159","DOIUrl":"https://doi.org/10.1021/acsbiomedchemau.5c00159","url":null,"abstract":"","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"475–483"},"PeriodicalIF":4.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.5c00159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863073","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":"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}