Bioorganic Chemistry最新文献_第10页

Structurally diverse tetrahydroxanthone analogues from Paraconiothyrium sp. AC31 with pyroptosis induction through targeted inhibition of PARP1 in hepatocellular carcinoma cells

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-26 DOI: 10.1016/j.bioorg.2025.108310

Meng-Ke Zhang , Qiao-Qiao Hu , Li-Ming He , Mu Li , Wei-Chen Chen , Kong-Kai Zhu , Rui-Ying Yuan , Xiao-Yan Wu , Ping Gao , Xiao-Bin Zeng , You-Sheng Cai

{"title":"Structurally diverse tetrahydroxanthone analogues from Paraconiothyrium sp. AC31 with pyroptosis induction through targeted inhibition of PARP1 in hepatocellular carcinoma cells","authors":"Meng-Ke Zhang , Qiao-Qiao Hu , Li-Ming He , Mu Li , Wei-Chen Chen , Kong-Kai Zhu , Rui-Ying Yuan , Xiao-Yan Wu , Ping Gao , Xiao-Bin Zeng , You-Sheng Cai","doi":"10.1016/j.bioorg.2025.108310","DOIUrl":"10.1016/j.bioorg.2025.108310","url":null,"abstract":"<div><div>This study reports the isolation and characterization of six novel tetrahydroxanthone derivatives, paraconixanthones A − F (<strong>1</strong>–<strong>6</strong>), a new diphenyl ether (<strong>7</strong>), and thirteen known compounds (<strong>8</strong>–<strong>20</strong>) from the endophytic fungus <em>Paraconiothyrium</em> sp. AC31. The chemical structures were elucidated using NMR, MS, X-ray diffraction, and ECD analyses. Paraconixanthones A and B (<strong>1</strong> and <strong>2</strong>) represent the first examples of tetrahydroxanthone-benzoate dimers, suggesting a unique biosynthetic pathway. Compound <strong>12</strong> exhibited potent anti-proliferative activity against HepG2 hepatocellular carcinoma cells (IC<sub>50</sub> = 1.19 μM), outperforming the standard therapy lenvatinib. Mechanistic studies revealed that compound <strong>12</strong> inhibits PARP1, leading to DNA damage, ROS accumulation, and caspase-3/GSDME-mediated pyroptosis. Additionally, it induces intrinsic apoptosis through BAX/BCL-2 modulation and caspase-7 activation. Meanwhile, GSDME deficiency treated with <strong>12</strong> exhibited the increased levels of PARP1 and caspase-3, supporting the cell death induced by <strong>12</strong> shifted from pyroptosis to apoptosis. These findings highlight the therapeutic potential of tetrahydroxanthones as selective agents targeting multiple cell death pathways in hepatocellular carcinoma, expanding the scope of natural product-based anti-cancer strategies.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108310"},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent advances of photocatalytic biochemical transformations

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-26 DOI: 10.1016/j.bioorg.2025.108320

Surabhi Sinha , Praveen P. Singh , Sudhanshu Kanaujia , Pravin K. Singh , Vishal Srivastava

引用次数: 0

Asperuloside promotes innate immunity via IRE-1/XBP-1 mediated unfolded protein response

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-26 DOI: 10.1016/j.bioorg.2025.108318

Hanlin Zhou , Yu Shen , Chunli Dong , Wentao Feng , Yuan Tian , Yi Xiao

{"title":"Asperuloside promotes innate immunity via IRE-1/XBP-1 mediated unfolded protein response","authors":"Hanlin Zhou , Yu Shen , Chunli Dong , Wentao Feng , Yuan Tian , Yi Xiao","doi":"10.1016/j.bioorg.2025.108318","DOIUrl":"10.1016/j.bioorg.2025.108318","url":null,"abstract":"<div><div>Numerous studies have reported that asperuloside (ASP), a monomeric compound extracted from the traditional Chinese medicine Spreading Hedyotis Herb, possesses a variety of medicinal properties, including the treatment of obesity, cancer, inflammatory diseases, and bacterial infections. However, its role in innate immunity and the underlying mechanisms of action remain largely unexplored. Protein homeostasis and the health of the endoplasmic reticulum (ER) are crucial for organismal function, as a well-balanced ER is essential not only for maintaining cellular integrity but also for ensuring immune homeostasis. In this study, we demonstrated that asperuloside enhances the resistance of <em>Caenorhabditis elegans</em> to the human opportunistic pathogen <em>Pseudomonas aeruginosa</em> PA14 and reduces the bacterial load within its intestine. Additionally, asperuloside promotes innate immunity by activating the IRE-1/XBP-1 signaling pathway. Furthermore, asperuloside protects A549 human lung epithelial cells and mice against PA14 infection through the IRE-1/XBP-1 signaling pathway. Our findings indicate that the ability of asperuloside to promote innate immunity is conserved across invertebrates and mammals, offering new insights for the future development of antibacterial drugs.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108318"},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of a novel Azaspirooxindolinone-based PROTAC for selective BTK degradation and enhanced anticancer activity

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-26 DOI: 10.1016/j.bioorg.2025.108316

Naveen Kumar Rampeesa , Rambabu Gundla , Gopal Mudasani , Sudhakar Tangallapalli , Sreenivasa Reddy Anugu , Soňa Gurská , Juan Bautista De Sanctis , Petr Džubák , Marián Hajdúch , Viswanath Das

{"title":"Identification of a novel Azaspirooxindolinone-based PROTAC for selective BTK degradation and enhanced anticancer activity","authors":"Naveen Kumar Rampeesa , Rambabu Gundla , Gopal Mudasani , Sudhakar Tangallapalli , Sreenivasa Reddy Anugu , Soňa Gurská , Juan Bautista De Sanctis , Petr Džubák , Marián Hajdúch , Viswanath Das","doi":"10.1016/j.bioorg.2025.108316","DOIUrl":"10.1016/j.bioorg.2025.108316","url":null,"abstract":"<div><div>Bruton's Tyrosine Kinase (BTK) is a key driver of hematological malignancies, autoimmune disorders, and neuroinflammation, making it an attractive therapeutic target. Proteolysis targeting chimeras (PROTACs) offer a novel strategy for BTK degradation via the E3 ubiquitin ligase pathway. Here, we evaluated nine azaspirooxindolinone-based PROTAC derivatives for their cytotoxicity and BTK-targeting activity. Several compounds exhibited potent cytotoxicity against BTK-high RAMOS lymphoma cells without affecting non-cancer fibroblasts or normal T/B-cell lymphocytes. Among them, PROTAC <strong>25</strong> emerged as the most effective degraded, achieving a Dmax of 72.84 % and DC50 of 0.27 μM in a proteasome-dependent manner. Although PROTAC <strong>25</strong> was cytotoxic to IL-2-inducible T cell Kinase (ITK)-positive cells, ITK protein levels remained unaffected. Furthermore, kinase assays revealed that PROTAC 25 inhibited BTK kinase activity (IC₅₀ = 0.44 μM) with moderate selectivity over ITK (IC₅₀ = 2.16 μM). Notably, PROTAC <strong>25</strong> suppressed BTK-mediated downstream signaling in RAMOS cells, as evidenced by reduced phosphorylation of BTK and its downstream effector, p38 MAPK. These findings highlight PROTAC <strong>25</strong> as a promising BTK degrader with therapeutic potential and underscore the value of azaspirooxindolinone-based PROTACs in targeting BTK-driven diseases.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108316"},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polar flagellin glycan heterogeneity of Aeromonas hydrophila strain ATCC 7966T

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-26 DOI: 10.1016/j.bioorg.2025.108300

Kelly M. Fulton , Elena Mendoza-Barberà , Juan M. Tomás , Susan M. Twine , Jeffrey C. Smith , Susana Merino

{"title":"Polar flagellin glycan heterogeneity of Aeromonas hydrophila strain ATCC 7966T","authors":"Kelly M. Fulton , Elena Mendoza-Barberà , Juan M. Tomás , Susan M. Twine , Jeffrey C. Smith , Susana Merino","doi":"10.1016/j.bioorg.2025.108300","DOIUrl":"10.1016/j.bioorg.2025.108300","url":null,"abstract":"<div><div>Motile pathogens often rely upon flagellar motility as an essential virulence factor and in many species the structural flagellin protein is glycosylated. Flagellin glycosylation has been shown to be important for proper function of the flagellar filament in a number of bacterial species. <em>Aeromonas hydrophila</em> is a ubiquitous aquatic pathogen with a constitutively expressed polar flagellum. Using a suite of mass spectrometry techniques, the flagellin FlaA and FlaB structural proteins of <em>A. hydrophila</em> strain ATCC 7966<sup>T</sup> were shown to be glycosylated with significant microheterogeneity, macroheterogeneity, and metaheterogeneity. The primary linking sugar in this strain was a novel and previously unreported pseudaminic acid derivative with a mass of 422 Da. The pseudaminic acid derivative was followed in sequence by two hexoses, an <em>N</em>-acetylglucosamine (with additional variable secondary modification), and a deoxy <em>N</em>-acetylglucosamine derivative. These pentasaccharide glycans were observed modifying all eight modification sites. Hexasaccharides, which included an additional <em>N</em>-acetylhexosamine residue as the capping sugar, were observed exclusively modifying a pair of isobaric peptides from FlaA and FlaB. Interestingly, these isobaric peptides are immediately adjacent to a toll-like receptor 5 binding site in both protein sequences. Glycosylation status was also linked to motility, a critical bacterial virulence factor.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"158 ","pages":"Article 108300"},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143580218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Morpholino nicotinamide analogs of ponatinib, dual MNK, p70S6K inhibitors, display efficacy against lung and breast cancers

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-26 DOI: 10.1016/j.bioorg.2025.108298

Riddhi Chaudhuri , Neetu Dayal , Joshua Kaiser , Rodrigo Mohallem , Nickolas R. Brauer , Kofi Simpa Yeboah , Uma K. Aryal , Herman O. Sintim

{"title":"Morpholino nicotinamide analogs of ponatinib, dual MNK, p70S6K inhibitors, display efficacy against lung and breast cancers","authors":"Riddhi Chaudhuri , Neetu Dayal , Joshua Kaiser , Rodrigo Mohallem , Nickolas R. Brauer , Kofi Simpa Yeboah , Uma K. Aryal , Herman O. Sintim","doi":"10.1016/j.bioorg.2025.108298","DOIUrl":"10.1016/j.bioorg.2025.108298","url":null,"abstract":"<div><div>Therapeutic options for aggressive cancer types such as breast and lung remain limited; disease relapse and death occur in 30–60% of non-small cell lung cancer (NSCLC) patients, whereas in triple-negative breast cancer or TNBC, recurrence-free survival occurs in less than 30% patients. The kinases, MNK and p70S6K have been proposed as targets for the potential treatment of breast cancer (BC) and lung cancer but currently, no drug that was purposely designed to inhibit these kinases have been approved by the FDA for the treatment of BC or NSCLC. In this study, we have identified <strong>HSND80</strong> (a morpholino nicotinamide analog of ponatinib) as a potent MNK/p70S6K inhibitor that has excellent activity against TNBC and NSCLC cell lines. <strong>HSND80</strong> has a longer target residence time (τ) of 45 mins and 58 mins against MNK1 and MNK2 respectively, compared to τ of eFT508 (tomivosertib) against MNK1 and MNK2 (τ = 1 min and 5 min, respectively). Molecular dynamics simulation was used to provide some insights into the binding of <strong>HSND80</strong> to MNK and p70S6K kinases. Western blotting analysis and phosphoproteomics analysis of the TNBC cell line, MDA-MB-231, revealed that phosphorylations of elF4E (MNK target) and elF4B and S6 (p70S6K targets) were reduced upon compound treatment, which is in line with the proposed mechanism of action; dual MNK/p70S6K targeting. <strong>HSND80</strong> could be dosed orally at 15 and 30 mg/kg and at such doses, could reduce tumor volume in a syngeneic NSCLC mouse model.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"159 ","pages":"Article 108298"},"PeriodicalIF":4.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis, and biological evaluation of novel artemisinin-based HDAC inhibitors with antitumor and antimalarial activities

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-25 DOI: 10.1016/j.bioorg.2025.108312

Jin He , Youyou He , Yunan Qian , Shuaibo Du , Ruikang Sun , Yujiao Liu , Jiping Yu , Yi Ding , Siyuan Zhou , Lubin Jiang , Shengzheng Wang

{"title":"Design, synthesis, and biological evaluation of novel artemisinin-based HDAC inhibitors with antitumor and antimalarial activities","authors":"Jin He , Youyou He , Yunan Qian , Shuaibo Du , Ruikang Sun , Yujiao Liu , Jiping Yu , Yi Ding , Siyuan Zhou , Lubin Jiang , Shengzheng Wang","doi":"10.1016/j.bioorg.2025.108312","DOIUrl":"10.1016/j.bioorg.2025.108312","url":null,"abstract":"<div><div>In addition to the clinical applications as antimalarial agents, artemisinin and its derivatives have demonstrated significant potential in antitumor drug discovery. To enhance antitumor activity, a novel series of artemisinin-containing histone deacetylase (HDAC) inhibitors was designed using a hybrid strategy that fused the artemisinin moiety with HDAC inhibitory functionality. A triazole ring was incorporated into the linker region to improve water solubility. Among these derivatives, compound <strong>Hj-9</strong> exhibited broad spectrum and especially potent antitumor activity against acute myelogenous leukemia cells MV4–11 (IC<sub>50</sub> = 0.38 μM). Mechanism studies revealed that <strong>Hj-9</strong> effectively arrests the cancer cell cycle at the G0/G1 phase and exhibits significant antiangiogenic activity. Further investigation demonstrated that <strong>Hj-9</strong> induces cell autophagy, apoptosis, and mitochondrial membrane potential changes. Enzyme inhibitory activities against HDAC isoforms indicated that <strong>Hj-9</strong> broadly inhibits multiple HDAC subtypes, especially showing particularly good inhibition of HDAC6. Furthermore, the antimalarial evaluation revealed derivatives <strong>Hj-1</strong>, <strong>Hj-2</strong> and <strong>Hj-9</strong> showed good antimalarial activity.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108312"},"PeriodicalIF":4.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of cadinane sesquiterpenoids as GOT1 inhibitors from Penicillium sp. HZ-5

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-25 DOI: 10.1016/j.bioorg.2025.108303

Yeting Zhang , Xinye Huang , Xinming Song , Xuan Li , Jinlong Zhang , Ming Chen , Zhengyi Shi , Binbin Song , Wei Wei , Changxing Qi , Yonghui Zhang

{"title":"Discovery of cadinane sesquiterpenoids as GOT1 inhibitors from Penicillium sp. HZ-5","authors":"Yeting Zhang , Xinye Huang , Xinming Song , Xuan Li , Jinlong Zhang , Ming Chen , Zhengyi Shi , Binbin Song , Wei Wei , Changxing Qi , Yonghui Zhang","doi":"10.1016/j.bioorg.2025.108303","DOIUrl":"10.1016/j.bioorg.2025.108303","url":null,"abstract":"<div><div>Fifteen new cadinane sesquiterpenoids, amorphaenes A–O (<strong>1</strong>–<strong>15</strong>), along with one known compound, were isolated from an endophytic fungus <em>Penicillium</em> sp. HZ-5 collected from <em>Hypericum wilsonii</em> N. Robson. Notably, compound <strong>7</strong> was the first example of 11-<em>nor</em> cadinane sesquiterpenoid <em>via</em> the oxidative cleavage between C-11 and C-13. Their structures were elucidated by extensive spectroscopic analysis, singlecrystal X-ray diffraction and ECD calculation and comparison. Significantly, compounds <strong>1</strong>, <strong>5</strong>, <strong>8</strong>, <strong>13</strong> and <strong>16</strong> exhibited glutamic oxaloacetate transaminase 1 (GOT1) inhibitory effects, with IC<sub>50</sub> values ranging from 20.0 ± 2.1 to 26.2 ± 2.7 <em>μ</em>M and also showed potential cytotoxicity on pancreatic ductal adenocarcinoma (PDAC) cells, with IC<sub>50</sub> values ranging from 13.1 ± 1.5 to 28.6 ± 2.9 <em>μ</em>M.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108303"},"PeriodicalIF":4.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of new aphidicolin diterpenoids from the deep-sea-derived fungus Botryotinia fuckeliana with cytotoxic activity against human bladder cancer cells

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-24 DOI: 10.1016/j.bioorg.2025.108311

Siwen Niu , Shuhuan Huang , Menglei Shi , Zhuhua Luo , Zongze Shao , Bihong Hong , Wenjing Tian

{"title":"Discovery of new aphidicolin diterpenoids from the deep-sea-derived fungus Botryotinia fuckeliana with cytotoxic activity against human bladder cancer cells","authors":"Siwen Niu , Shuhuan Huang , Menglei Shi , Zhuhua Luo , Zongze Shao , Bihong Hong , Wenjing Tian","doi":"10.1016/j.bioorg.2025.108311","DOIUrl":"10.1016/j.bioorg.2025.108311","url":null,"abstract":"<div><div>Aphidicolin, characterized by a highly fused 6/6/5/6 tetracyclic diterpenoid skeleton, had been explored as a potential anticancer drug in clinical trials. However, its development has been constrained by poor solubility. The discovery of new aphidicolin derivatives offers promising prospects for anticancer drug development. In the present study, 37 new aphidicolin derivatives, designated as aphidicolins B1–B37 (<strong>1</strong>–<strong>37</strong>), together with 34 known analogues (<strong>38</strong>–<strong>71</strong>), were discovered from the ethyl acetate (EtOAc) extract of the deep-sea-derived fungus <em>Botryotinia fuckeliana</em>. Their structures, including absolute configurations, were determined by extensive analyses of spectroscopic data, the phenylglycine methyl ester (PGME) method, modified Mosher's method, and comparison of experimental and calculated electronic circular dichroism (ECD) data. Notably, aphidicolin B12 (<strong>12</strong>) features a 6/6/5/6/6 pentacyclic framework with an unprecedented <em>γ</em>-lactone ring E, while compound <strong>31</strong> contains a novel 6/6/5/6/5/5 hexacyclic system bearing an unprecedented tetrahydrofuran ring formed by an ether bridge between C-3 and C-6. All isolated aphidicolins were evaluated for their cytotoxic effects against T24 human bladder cancer cells. Among them, 11 diterpenoids showed stronger inhibitory activity than aphidicolin (<strong>60</strong>), especially compound <strong>32</strong>, which exhibited an IC<sub>50</sub> value of 1.9 μM, significantly more potent than <strong>60</strong> (IC<sub>50</sub> = 27.6 μM). The structure-bioactivity relationships were also discussed. Further mechanistic studies revealed that <strong>32</strong> inhibits T24 cells proliferation by inducing cell cycle arrest in the G0/G1 phase, suggesting its potential as a therapeutic agent for bladder cancer treatment.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108311"},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and physicochemical properties of new phosphoramide oligodeoxyribonucleotides. I. N-caffeine derivatives

IF 4.5 2区医学

Bioorganic Chemistry Pub Date : 2025-02-24 DOI: 10.1016/j.bioorg.2025.108313

Alina I. Novgorodtseva , Aleksey Y. Vorob'ev , Alexander A. Lomzov , Svetlana V. Vasilyeva

{"title":"Synthesis and physicochemical properties of new phosphoramide oligodeoxyribonucleotides. I. N-caffeine derivatives","authors":"Alina I. Novgorodtseva , Aleksey Y. Vorob'ev , Alexander A. Lomzov , Svetlana V. Vasilyeva","doi":"10.1016/j.bioorg.2025.108313","DOIUrl":"10.1016/j.bioorg.2025.108313","url":null,"abstract":"<div><div>Herein, we report the synthesis of new oligonucleotide derivatives containing an internucleotide <em>N</em>-caffeine phosphoramide (P<em>N</em>-caffeine) group. This modification was introduced via Staudinger's reaction with an appropriate caffeine azide during standard solid-phase oligonucleotide synthesis. Modified hexathymidylates and oligonucleotides with a heteronucleotide sequence were obtained with a yield of ∼90 %. Physicochemical properties of the new oligonucleotides were analyzed next. UV spectral determination of pK<sub>a</sub> showed that the P<em>N</em>-caffeine group is neutral at pH < 5 and is negatively charged at pH > 8. The modified oligonucleotides emit weak fluorescence, and the same is true for different charge states of the P<em>N</em>-caffeine moiety and its positions in the DNA strand. A decrease in melting temperature of DNA/DNA and DNA/RNA duplexes was observed after the modification introduction into the DNA. Circular dichroism analysis indicated that the modification does not significantly disrupt either a DNA/DNA or DNA/RNA duplex at either low or high temperatures. This modification expands the existing classes of phosphoramide derivatives of nucleic acids and can be used for various biomedical applications.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108313"},"PeriodicalIF":4.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0