Dr. Kathrin Bellmann-Sickert

Dr. Kathrin Bellmann-Sickert

Telefon:
+49 341 97 36839

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Chemical peptide modification in GPCR signaling

Peptides have a high potential as pharmaceuticals as they can target protein-protein interactions in more specific manner compared to small molecules. Chemical modification by coupling „unnatural“ entities to the peptide aids in stabilization, resorption and distribution of peptide pharmaceuticals in the organism. However, these modifications also influence the pharmacological effects of a peptide ligand at its target molecule. For instance, we found, that PEGylation could effectively bias the signaling of a peptidic GPCR balanced agonist towards G-protein signaling, while lipidation led to higher arrestin recruitment and internalization of the same ligand. Inducing specific signaling pathways over others has the advantage, that a potential peptide drug shows less side effects and targets only the pathway needed for treating the respective pathology. In our research, we aim to find structural requirements for the ligand receptor interaction, that lead to the induction of different signaling pathways. Recently, we showed that carboranylation could induce arrestin recruitment in a short neuropeptide Y analogue, that on its own produced only G-protein signaling. This points to the existence of a binding pocket in the target receptor, that is responsible for arrestin-mediated signaling. In order to investigate this, we employ chemical synthesis and modification of peptide GPCR ligands, structural investigations of our ligand at the receptor as well as computational methods for modeling ligand binding pockets. That way, we hope to elucidate rational ways on how to design ligands for peptide GPCRs with specific signaling outcome.

Publikationen

2018

Valeria Castelleto, Ian W. Hamley, Jani Seitsonen, Janne Ruokolainen, Gemma Harris, Kathrin Bellmann-Sickert, Annette G. Beck-Sickinger (2018) Conformation and Aggregation of Selectively PEGylated and Lipidated Gastric Peptide Hormone Human PYY3-36. Biomacromolecules, 19, 4320-4332.AbstractPDF
Sven Hofmann, Josephin Lindner, Annette G. Beck-Sickinger, Evamarie Hey-Hawkins, Kathrin Bellmann-Sickert (2018) Carbaboranylation of truncated C-terminal neuropeptide Y analogue leads to full hY1 receptor agonism. ChemBioChem., 19, 2300–2306.AbstractPDF
Milos Erak, Kathrin Bellmann-Sickert, Sylvia Els-Heindl, Annette G. Beck-Sickinger (2018) Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics. Bioorg. Med. Chem., 26, 2759-2765.AbstractPDF
Sarah Zernia, Ronny Frank, Renato H.-J. Weiße, Heinz-Georg Jahnke, Kathrin Bellmann-Sickert, Andrea Prager, Bernd Abel, Norbert Sträter, Andrea Robitzki, Annette G. Beck-Sickinger (2018) Surface-Binding Peptide Facilitates Electricity-Driven NADPH-Free Cytochrome P450 Catalysis. ChemCatChem., 10, 525-530.AbstractPDF

2016

Veronika Thieme, Navjeet Jolly, Andreas N. Madsen, Kathrin Bellmann-Sickert, Thue Schwartz, Birgitte Holst, Helen M. Cox and Annette G. Beck-Sickinger (2016) High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice. Br. J. Pharmacol. 173, 3208-3221.AbstractPDF
Nydia Panitz, Stephan Theisgen, Sergey A. Samsonov, Jan-Philip Gehrcke, Lars Baumann, Kathrin Bellmann-Sickert, Sebastian Köhling, M Teresa Pisabarro, Jörg Rademann, Daniel Huster and Annette G. Beck-Sickinger (2016) The structural investigation of glycosaminoglycan binding to CXCL12 displays distinct interaction sites. Glycobiology. 26, 1209-1221.AbstractPDF
Cecilia Ratner, Louise J. Skov, Zindy Raida, Thomas Bächler, Kathrin Bellmann-Sickert, Christelle Le Foll, Bjørn Sivertsen, Louise S. Dalbøge, Bolette Hartmann, Annette G. Beck-Sickinger, Andreas N. Madsen, Jacob Jelsing, Jens J. Holst, Thomas A. Lutz, Zane B. Andrews and Birgitte Holst (2016) Effects of Peripheral Neurotensin on Appetite Regulation and Its Role in Gastric Bypass Surgery. Endocrinology. 157, 3482-3492.AbstractPDF
Dilip Verma, B. Hörmer, Kathrin Bellmann-Sickert, Veronika Theime, Annette G. Beck-Sickinger, Herbert Herzog, Günther Sperk and Ramon O Tasan (2016) Pancreatic polypeptide  and its central Y4 receptors are essential for cued fear extinction and permanent suppression. Br. J. Pharmacol. 173, 1925-1938.AbstractPDF
Sarah Zernia, Florian Ott, Kathrin Bellmann-Sickert, René Frank, Marcus Klenner, Heinz-Georg Jahnke, Andrea Prager, Bernd Abel, Andrea Robitzki and Annette G. Beck-Sickinger (2016) Peptide-mediated specific immobilization of catalytically active Cytochrome P450 BM3 variant. Bioconjug. Chem. 27, 1090-1097.AbstractPDF
Sylvia Els-Heindl, Kathrin Bellmann-Sickert and Annette G. Beck-Sickinger (2016) C-terminus of a hexapeptidic ghrelin receptor inverse agonist can switch peptide behaviour from inverse agonism to agonism. Biopolymers, 106, 101-108.AbstractPDF

2015

Kathrin Bellmann-Sickert, Tracy A. Stone, Bradley E. Poulsen, Charles M. Deber (2015) Efflux by small multidrug resistance proteins is inhibited by membrane-interactive helix-stapled peptides. J. Biol. Chem. 290,1752-1759AbstractPDF

2014

Veronika Mäde, Kathrin Bellmann-Sickert, Anette Kaiser, Jens Meiler and Annette G. Beck-Sickinger (2014) Position and length of fatty acids strongly affect receptor selectivity pattern of human pancreatic polypeptide analogues. ChemMedChem 9, 2463-74AbstractPDF
Veronika Mäde, Stefanie Babilon, Navjeet Jolly, Lizzy Wanka, Kathrin Bellmann-Sickert, Luis E. Diaz Gimenez, Karin Mörl, Helen M. Cox, Vsevolod V. Gurevich and Annette G. Beck-Sickinger (2014) Peptide modifications differentially alter G protein-coupled receptor internalization and signaling bias. Angew. Chem. Int. Ed. 53, 10067-71AbstractPDF

2011

Kathrin Bellmann-Sickert and Annette G. Beck-Sickinger (2011) Palmitoylated SDF1α Shows Increased Resistance Against Proteolytic Degradation in Liver Homogenates, ChemMedChem.6, 193-200.AbstractPDF
Kathrin Bellmann-Sickert, Christian Elling, Andreas Nygaard Madsen, Paul B. Little, Karsten Lundgren, Lars-Ole Gerlach, Ralf Bergmann, Birgitte Holst, Thue W. Schwartz, Annette G. Beck Beck-Sickinger (2011) Long-acting Lipidated Analogue of Human Pancreatic Polypeptide is Slowly Released into Circulation,  J. Med. Chem. 54, 2658-67AbstractPDF

2010

Kathrin Bellmann-Sickert, Lars Baumann, Annette G. Beck-Sickinger (2010) Selective labelling of stromal cell-derived factor 1α with carboxyfluorescein to study receptor internalisation, J. Pept. Sci. 16, 568-574.AbstractPDF

2009

Knut Kölbel, Christian Ihling, Kathrin Bellmann-Sickert, Ines Neundorf, Annette G. Beck-Sickinger, Andrea Sinz, Uwe Kühn and Elmar Wahle (2009) Type I arginine methyl transferases PRMT1 and 3 act distributively, J. Biol. Chem. 284, 8274-8282.AbstractPDF

Reviews

Sven Hofmann, Kathin Bellmann-Sickert, Annette G. Beck-Sickinger (2019) Chemical Modification of Neuropeptide Y for Human Y1 Receptor Targeting in Health and Disease. Biol. Chem., doi:10.1515/hsz-2018-0364. [Epub ahead of print]AbstractPDF
Milos Erak, Kathrin Bellmann-Sickert, Sylvia Els-Heindl and Annette G. Beck-Sickinger (2018) Peptide chemistry toolbox - transforming natural peptides into peptide therapeutics, Bioorg. Med. Chem. doi:10.1016/j.bmc.2018.01.012 [Epub ahead of print] AbstractPDF
Verena Ahrens, Kathrin Bellmann-Sickert and Annette G. Beck-Sickinger (2012) Peptides and Peptide Conjugates: Therapeutics on the Upward Path. Future Med. Chem. 4, 1567-1586.AbstractPDF
Kathrin Bellmann-Sickert, Annette G. Beck-Sickinger (2010) Peptide Drugs to Target G-Protein Coupled Receptors. Trends Pharm. Sci. 31, 434-441. AbstractPDF
letzte Änderung: 05.03.2020

Kontakt

Dr. Kathrin Bellmann-Sickert
Brüderstraße 34
04103 Leipzig

Telefon: +49 341 97 36839
Telefax: +49 341 97 36909
E-Mail