Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Méndez, Y.; Vasco, A. V.; Ebensen, T.; Schulze, K.; Yousefi, M.; Davari, M. D.; Wessjohann, L. A.; Guzmán, C. A.; Rivera, D. G.; Westermann, B.;Diversification of a novel α‐galactosyl ceramide hotspot boosts the adjuvant properties in parenteral and mucosal vaccinesAngew. Chem. Int. Ed.63e202310983(2024)DOI: 10.1002/anie.202310983
The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α‐galactosyl ceramide (α‐GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B‐cell activation. Herein, we introduce a novel derivatization hotspot at the α‐GalCer skeleton, namely the N‐substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self‐adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen‐specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α‐GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α‐GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.
Publikation
Püllmann, P.; Homann, D.; Karl, T. A.; König, B.; Weissenborn, M. J.;Light‐controlled biocatalysis by unspecific peroxygenases with genetically encoded photosensitizersAngew. Chem. Int. Ed.62e202307897(2023)DOI: 10.1002/anie.202307897
Fungal unspecific peroxygenases (UPOs) have gained substantial attention for their versatile oxyfunctionalization chemistry paired with impressive catalytic capabilities. A major drawback, however, remains their sensitivity towards their co‐substrate hydrogen peroxide, necessitating the use of smart in situ hydrogen peroxide generation methods to enable efficient catalysis setups. Herein, we introduce flavin‐containing protein photosensitizers as a new general tool for light‐controlled in situ hydrogen peroxide production. By genetically fusing flavin binding fluorescent proteins and UPOs, we have created two virtually self‐sufficient photo‐enzymes (PhotUPO). Subsequent testing of a versatile substrate panel with the two divergent PhotUPOs revealed two stereoselective conversions. The catalytic performance of the fusion protein was optimized through enzyme and substrate loading variation, enabling up to 24300 turnover numbers (TONs) for the sulfoxidation of methyl phenyl sulfide. The PhotUPO concept was upscaled to a 100 mg substrate preparative scale, enabling the extraction of enantiomerically pure alcohol products.Graphical Abstract
Unspecific peroxygenases (UPOs) have recently gained
attraction as versatile oxyfunctionalization catalysts. One shortcoming,
however, is their susceptibility towards the co-substrate hydrogen
peroxide. As a solution, the concept of light-dependent UPO biocatalysis
with genetically encoded flavin-containing photosensitizer proteins for
in situ hydrogen peroxide production is introduced.
Publikation
Herres-Pawlis, S.; Bach, F.; Bruno, I. J.; Chalk, S. J.; Jung, N.; Liermann, J. C.; McEwen, L. R.; Neumann, S.; Steinbeck, C.; Razum, M.; Koepler, O.;Minimum information standards in chemistry: A call for better research data management practicesAngew. Chem. Int. Ed.61e202203038(2022)DOI: 10.1002/anie.202203038
Research data management (RDM) is needed to assist experimental advances and data collection in the chemical sciences. Many funders require RDM because experiments are often paid for by taxpayers and the resulting data should be deposited sustainably for posterity. However, paper notebooks are still common in laboratories and research data is often stored in proprietary and/or dead-end file formats without experimental context. Data must mature beyond a mere supplement to a research paper. Electronic lab note-books (ELN) and laboratory information managementsystems (LIMS) allow researchers to manage data better and they simplify research and publication. Thus, an agreement is needed on minimum information standards for data handling to support structured approaches to data reporting. As digitalization becomes part of curricular teaching, future generations of digital native chemists will embrace RDM and ELN as an organic part of their research.
Publikation
Drača, D.; Edeler, D.; Saoud, M.; Dojčinović, B.; Dunđerović, D.; Đmura, G.; Maksimović-Ivanić, D.; Mijatović, S.; Kaluđerović, G. N.;Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studiesJ. Inorg. Biochem.217111383(2021)DOI: 10.1016/j.jinorgbio.2021.111383
CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in lower μM range. The activity of SBA-15|CP was found similar to the activity of CP alone. Both CP and SBA-15|CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4′,6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2′,7′-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15|CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15|CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15|CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15|CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP.