Osman Gani

• Nolsøe, Jens Mortansson Jelstrup; Underhaug, Jarl; Sørskår, Åshild Moi; Antonsen, Simen; Malterud, Karl Egil & Gani, Osman [Vis alle 11 forfattere av denne artikkelen] (2024). Biological Evaluations, NMR Analyses, Molecular Modeling Studies, and Overview of the Synthesis of the Marine Natural Product (−)-Mucosin . Molecules. ISSN 1431-5157. 29(5). doi: 10.3390/molecules29050994. Fulltekst i vitenarkiv Vis sammendrag

  Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (−)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (−)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (−)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (−)-mucosin (1) is also presented.

• Hodnekvam, Kristin; Iversen, Hilde H.; Gani, Osman; Brunborg, Cathrine & Skrivarhaug, Torild (2023). Do adolescents and emerging adults receive the diabetes care they truly need? A nationwide study of the quality of diabetes health care during the transition from paediatric to adult care. Diabetic Medicine. ISSN 0742-3071. 40(7). doi: 10.1111/dme.15091.
• Birkebaek, Niels H; Kamrath, Clemens; Grimsmann, Julia M; Aakesson, Karin; Cherubini, Valentino & Dovc, Klemen [Vis alle 26 forfattere av denne artikkelen] (2022). Impact of the COVID-19 pandemic on long-term trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes: an international multicentre study based on data from 13 national diabetes registries. The Lancet Diabetes and Endocrinology. ISSN 2213-8587. 10(11), s. 786–794. doi: 10.1016/S2213-8587(22)00246-7.
• Lanzinger, Stefanie; Zimmermann, Anthony; Ranjan, Ajenthen G.; Gani, A B S M Osman; Pons Perez, Saira & Akesson, Karin [Vis alle 21 forfattere av denne artikkelen] (2022). A collaborative comparison of international pediatric diabetes registries. Pediatric Diabetes. ISSN 1399-543X. 23(6), s. 627–640. doi: 10.1111/pedi.13362. Fulltekst i vitenarkiv
• Rødevand, Linn ; Bahrami, Shahram; Frei, Oleksandr; Lin, Aihua; Gani, Osman & Shadrin, Alexey A. [Vis alle 18 forfattere av denne artikkelen] (2021). Polygenic overlap and shared genetic loci between loneliness, severe mental disorders, and cardiovascular disease risk factors suggest shared molecular mechanisms. Translational Psychiatry. ISSN 2158-3188. 11(1). doi: 10.1038/s41398-020-01142-4. Fulltekst i vitenarkiv Vis sammendrag

  Clinical and epidemiological evidence suggest that loneliness is associated with severe mental disorders (SMDs) and increases the risk of cardiovascular disease (CVD). However, the mechanisms underlying the relationship between loneliness, SMDs, and CVD risk factors remain unknown. Here we explored overlapping genetic architecture and genetic loci shared between SMDs, loneliness, and CVD risk factors. We analyzed large independent genome-wide association study data on schizophrenia (SCZ), bipolar disorder (BD), major depression (MD), loneliness and CVD risk factors using bivariate causal mixture mode (MiXeR), which estimates the total amount of shared variants, and conditional false discovery rate to evaluate overlap in specific loci. We observed substantial genetic overlap between SMDs, loneliness and CVD risk factors, beyond genetic correlation. We identified 149 loci jointly associated with loneliness and SMDs (MD n = 67, SCZ n = 54, and BD n = 28), and 55 distinct loci jointly associated with loneliness and CVD risk factors. A total of 153 novel loneliness loci were found. Most of the shared loci possessed concordant effect directions, suggesting that genetic risk for loneliness may increase the risk of both SMDs and CVD. Functional analyses of the shared loci implicated biological processes related to the brain, metabolic processes, chromatin and immune system. Altogether, the study revealed polygenic overlap between loneliness, SMDs and CVD risk factors, providing new insights into their shared genetic architecture and common genetic mechanisms.

• Shadrin, Alexey A.; Frei, Oleksandr; Smeland, Olav Bjerkehagen; Bettella, Francesco; O`Connell, Kevin & Gani, Osman [Vis alle 12 forfattere av denne artikkelen] (2020). Phenotype-specific differences in polygenicity and effect size distribution across functional annotation categories revealed by AI-MiXeR. Bioinformatics. ISSN 1367-4803. doi: 10.1093/bioinformatics/btaa568. Fulltekst i vitenarkiv
• Alam, Kazi Asraful; Gani, Osman & Engh, Richard Alan (2020). Inhibitor binding of mutants of protein kinase A with GGGXXG and GXGXXA glycine-rich loop motifs. Journal of Molecular Recognition. ISSN 0952-3499. 2020. doi: 10.1002/jmr.2882.
• De Santi, Concetta; Gani, Osman A. B. S. M.; Helland, Ronny & Williamson, Adele Kim (2017). Structural insight into a CE15 esterase from the marine bacterial metagenome. Scientific Reports. ISSN 2045-2322. 7:17278, s. 1–10. doi: 10.1038/s41598-017-17677-4. Fulltekst i vitenarkiv
• Narayanan, Dilip; Gani, Osman; Gruber, Franz & Engh, Richard Alan (2017). Data driven polypharmacological drug design for lung cancer: Analyses for targeting ALK, MET, and EGFR. Journal of Cheminformatics. ISSN 1758-2946. 9(43), s. 1–19. doi: 10.1186/s13321-017-0229-8. Fulltekst i vitenarkiv
• Gani, Osman A.B.S.M.; Thakkar, Balmukund; Narayanan, Dilip; Alam, Kazi Asraful; Kyomuhendo, Peter & Rothweiler, Ulli [Vis alle 8 forfattere av denne artikkelen] (2015). Assessing protein kinase target similarity: Comparing sequence, structure, and cheminformatics approaches. Biochimica et Biophysica Acta - Proteins and Proteomics. ISSN 1570-9639. 1854(10), s. 1605–1616. doi: 10.1016/j.bbapap.2015.05.004.
• Gani, Osman A.B.S.M.; Narayanan, Dilip & Engh, Richard Alan (2013). Evaluating the Predictivity of Virtual Screening for Abl Kinase Inhibitors to Hinder Drug Resistance. Chemical Biology and Drug Design (CB&DD). ISSN 1747-0277. 82(5), s. 506–519. doi: 10.1111/cbdd.12170. Fulltekst i vitenarkiv Vis sammendrag

  Virtual screening methods are now widely used in early stages of drug discovery, aiming to rank potential inhibitors. However, any practical ligand set (of active or inactive compounds) chosen for deriving new virtual screening approaches cannot fully represent all relevant chemical space for potential new compounds. In this study, we have taken a retrospective approach to evaluate virtual screening methods for the leukemia target kinase ABL1 and its drug-resistant mutant ABL1-T315I. ‘Dual active’ inhibitors against both targets were grouped together with inactive ligands chosen from different decoy sets and tested with virtual screening approaches with and without explicit use of target structures (docking). We show how various scoring functions and choice of inactive ligand sets influence overall and early enrichment of the libraries. Although ligand-based methods, for example principal component analyses of chemical properties, can distinguish some decoy sets from active compounds, the addition of target structural information via docking improves enrichment, and explicit consideration of multiple target conformations (i.e. types I and II) achieves best enrichment of active versus inactive ligands, even without assuming knowledge of the binding mode. We believe that this study can be extended to other therapeutically important kinases in prospective virtual screening studies.

• Åberg, espen; Lund, Bjarte Aarmo; Pflug, Alexander; Gani, Osman A.B.S.M.; Rothweiler, Ulli & Oliveira, Taiana Maia De [Vis alle 7 forfattere av denne artikkelen] (2012). Structural origins of AGC protein kinase inhibitor selectivities: PKA as a drug discovery tool. Biological chemistry. ISSN 1431-6730. 393(10), s. 1121–1129. doi: 10.1515/hsz-2012-0248.
• Gani, Osman A.B.S.M. & Engh, Richard Alan (2010). Protein kinase inhibition of clinically important staurosporine analogues. Natural product reports (Print). ISSN 0265-0568. 27(4), s. 489–498. doi: 10.1039/b923848b.
• Odlo, Kristin; Fournier-Dit-Chabert, Jérémie; Ducki, Sylvie; Gani, Osman A.B.S.M.; Sylte, Ingebrigt & Hansen, Trond Vidar (2010). 1,2,3-Triazole analogs of combretastatin A-4 as potential microtubule-binding agents. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 18(18), s. 6874–6885. doi: 10.1016/j.bmc.2010.07.032.
• Gani, Osman A.B.S.M. & Sylte, Ingebrigt (2009). Molecular recognition of long chain fatty acids by peroxisome proliferator-activated receptor alpha. Medicinal Chemistry Research. ISSN 1054-2523. 18(1), s. 8–19. doi: 10.1007/s00044-008-9102-7.
• Gani, Osman A.B.S.M.; Adekoya, Olayiwola; Giurato, L; Spyrakis, F; Cozzini, P & Guccione, S [Vis alle 8 forfattere av denne artikkelen] (2008). Theoretical calculations of the catalytic triad in short-chain alcohol dehydrogenases/reductases. Biophysical Journal. ISSN 0006-3495. 94. doi: 10.1529/biophysj.107.111096.
• Gani, Osman A.B.S.M. & Sylte, Ingebrigt (2008). Ligand-induced stabilization and activation of peroxisome proliferator-activated receptor gamma. Chemical Biology and Drug Design (CB&DD). ISSN 1747-0277. 72, s. 50–57. doi: 10.1111/j.1747-0285.2008.00677.x.
• Odlo, K; Hentzen, J; dit Chabert, JF; Ducki, S; Gani, Osman A.B.S.M. & Sylte, Ingebrigt [Vis alle 10 forfattere av denne artikkelen] (2008). 1,5-disubstituted 1,2,3-triazoles as cis-restricted analogues of combretastatin A-4: Synthesis, molecular modeling and evaluation as cytotoxic agents and inhibitors of tubulin. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 16, s. 4829–4838. doi: 10.1016/j.bmc.2008.03.049.
• Gani, Osman A.B.S.M. & Sylte, Ingebrigt (2008). Molecular recognition of docosahexaenoic acid by peroxisome proliferator-activated receptors and retinoid-X receptor alpha. Journal of Molecular Graphics and Modelling. ISSN 1093-3263. 27, s. 217–224. doi: 10.1016/j.jmgm.2008.04.008.
• Gani, Osman A.B.S.M. (2008). Are fish oil omega-3 long-chain fatty acids and their derivatives peroxisome proliferator-activated receptor agonists? Cardiovascular Diabetology. ISSN 1475-2840. 7. doi: 10.1186/1475-2840-7-6.
• Gani, Osman A.B.S.M. (2007). Signposts of docking and scoring in drug design. Chemical Biology and Drug Design (CB&DD). ISSN 1747-0277. 70, s. 360–365. doi: 10.1111/j.1747-0285.2007.00571.x.

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• Thakkar, Balmukund; Gani, Osman & Engh, Richard Alan (2016). Practical Applications of Informatics Tools to Identify Drug Targets for Novel Compounds from Bio- and Chemoprospecting.
• Boomgaren, Marc; Gani, Osman; Engh, Richard Alan & Hansen, Jørn H (2016). Bioactive Heterocycle Libraries for Anticancer Drug Discovery - Development of Covalent Binding TK Inhibitors.
• Boomgaren, Marc; Gani, Osman A.B.S.M.; Engh, Richard Alan & Hansen, Jørn H (2015). Bioactive Heterocycle Libraries for Anticancer Drug Discovery.
• Gani, Osman A.B.S.M. & Sylte, Ingebrigt (2006). Molecular recognition of fatty acids by PPAR-alpha.
• Adekoya, Olayiwola Adedotun; Dahl, Svein G.; Gabrielsen, Mari; Gani, Osman A.B.S.M.; Khan, Mahmud Tareq Hassan & Kristiansen, kurt [Vis alle 10 forfattere av denne artikkelen] (2006). The molecular modelling group.
• Gani, Osman A.B.S.M. & Sylte, Ingebrigt (2006). Molecular recognition of fatty acids by PPAR-alpha.
• Gani, Osman A.B.S.M. & Sylte, Ingebrigt (2006). The effect of E-Z isomerization of docosahexaeonic acid (DHA) double bonds on binding to nuclear receptors.

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