title: Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol.
abstract: This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50-8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs.
authors: Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras , GR-26500 Patras, Greece.
authors: S
authors: S
authors: Fili
authors: Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras , GR-26500 Patras, Greece.
authors: A
authors: A
authors: Valmas
authors: Diabetes Protein Engineering, Novo Nordisk A/S , Novo Nordisk Park, DK-2760 Malov, Denmark.
authors: M
authors: M
authors: Norrman
authors: Diabetes Protein Engineering, Novo Nordisk A/S , Novo Nordisk Park, DK-2760 Malov, Denmark.
authors: G
authors: G
authors: Schluckebier
authors: PANalytical B.V. , Lelyweg 1, 7602 EA Almelo, The Netherlands.
authors: D
authors: D
authors: Beckers
authors: PANalytical B.V. , Lelyweg 1, 7602 EA Almelo, The Netherlands.
authors: T
authors: T
authors: Degen
authors: European Synchrotron Radiation Facility , CS40220, F-38043 Grenoble CEDEX 9, France.
authors: J
authors: J
authors: Wright
authors: European Synchrotron Radiation Facility , CS40220, F-38043 Grenoble CEDEX 9, France.
authors: A
authors: A
authors: Fitch
authors: Excelsus Structural Solutions , Belgium.
authors: F
authors: F
authors: Gozzo
authors: Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras , GR-26500 Patras, Greece.
authors: A E
authors: AE
authors: Giannopoulou
authors: Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras , GR-26500 Patras, Greece.
authors: F
authors: F
authors: Karavassili
authors: Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras , GR-26500 Patras, Greece.
authors: I
authors: I
authors: Margiolaki
keywords: 4-ethylresorcinol; X-ray diffraction; diabetes; human insulin; pH variation; powder diffraction; synchrotron radiation