TY - JOUR A1 - Faust, Kirstin A1 - Freitag, Nancy A1 - Barrientos, Gabriela A1 - Hartel, Christoph A1 - Blois, Sandra M. T1 - Galectin-Levels Are Elevated in Infants Born Preterm Due to Amniotic Infection and Rapidly Decline in the Neonatal Period JF - Frontiers in Immunology N2 - Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials. KW - galectin-1 KW - galectin-3 KW - galectin-9 KW - preterm infants KW - amniotic infection Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230701 SN - 1664-3224 VL - 11 ER - TY - THES A1 - Bertleff-Zieschang, Nadja Luisa T1 - Galectin-1: A Synthetic and Biological Study of a Tumor Target T1 - Galectin-1: Eine Synthetische und Biologische Studie eines Tumortargets N2 - Galectin-1 (hGal-1) is overexpressed by numerous cancer types and previously conducted studies confirmed that the β-galactoside-binding protein mediates various molecular interactions associated with tumor growth, spread and survival. Upon interaction with carbohydrate-based binding epitopes of glycan structures on human cell surfaces galectin-1 induces proliferative, angiogenetic and migratory signals and modulates negative T cell regulation which essentially helps the tumor to evade the immune response. These findings attributed galectin-1 a pivotal role in tumor physiology and strongly suggest the protein as target for diagnostic and therapeutic applications. Within the scope of this work a strategy was elaborated for designing tailor-made galectin-1 ligands by functionalizing selected hydroxyl groups of the natural binding partner N-acetyllactosamine (LacNAc) that are not involved in the sophisticated interplay between the disaccharide and the protein. Synthetic modifications intended to introduce chemical groups i) to address a potential binding site adjacent to the carbohydrate recognition domain (CRD) with extended hGal-1-ligand interactions, ii) to implement a tracer isotope for diagnostic detection and iii) to install a linker unit for immobilization on microarrays. Resulting structures were investigated regarding their targeting ability towards galectin-1 by cocrystallization experiments, SPR and ITC studies. Potent binders were further probed for their diagnostic potential to trace elevated galectin-1 levels in microarray experiments and for an application in positron emission tomography (PET). N2 - Galectin-1 (hGal-1) wird von zahlreichen Tumoren überexprimiert und frühere Studien bestätigten, dass das β-Galactosid-bindende Protein verschiedene molekulare Wechselwirkungen vermittelt, welche in direktem Zusammenhang mit Tumorwachstum, -ausbreitung und -überleben stehen. Durch die Wechselwirkung mit Kohlenhydrat-basierten Bindungsepitopen von Glykanstrukturen auf Zelloberflächen induziert Galectin-1 proliferative, angiogenetische und migratorische Signale und moduliert die negative Regulierung von T-Zellen, entscheidend für den Tumor, um der Immunantwort zu entkommen. Diese Beobachtungen schreiben Galectin-1 eine zentrale Rolle in der Tumorphysiologie zu, was dieses Protein zu einem attraktiven Target für diagnostische und therapeutische Anwendungen macht. Im Rahmen dieser Arbeit wurde eine Synthesestrategie für das Design maßgeschneiderter Galectin-1 Liganden entwickelt, wobei ausgewählte Hydroxylgruppen des natürlichen Bindungspartners N-Acetyllactosamin (LacNAc), welche nicht an dem hochkomplexen Zusammenspiel zwischen Protein und Disaccharid beteiligt sind, funktionalisiert wurden. Synthetische Modifikationen wurden mit der Absicht eingeführt i) eine potentielle Bindungstasche in Nachbarschaft der Kohlenhydraterkennungsdomäne (CRD) zu adressieren, ii) einen Isotopenmarker für die diagnostische Detektion zu implementieren und iii) eine Brückeneinheit zu integrieren, welche einer späteren Immobilisierung auf Mikroarrays dient. Resultierende Strukturen wurden mittels Kokristallisationsexperimenten, SPR- und ITC-Studien auf ihre Fähigkeit untersucht, Galectin-1 zu adressieren. Erfolgreich entwickelte Liganden wurden zudem auf ihr diagnostisches Potential getestet, erhöhte Galectin-1-Spiegel in Microarray-Experimenten zu detektieren und könnten zukünftig Einsatz in der Positronen-Emissions-Tomographie (PET) finden. KW - Organische Synthese KW - Galectine KW - Kohlenhydrate KW - Molekulare Erkennung KW - Click-Chemie KW - carbohydrate chemistry KW - protein crystallography KW - galectin-1 KW - protein-ligand-interaction KW - N-acetyllactosamine Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-101529 ER -