The T₂ structure of polycrystalline cubic human insulin

Abstract

The polymorphism of human insulin upon pH variation was characterized via X-ray powder diffraction, employing a crystallization protocol previously established for co-crystallization with phenolic derivatives. Two distinct rhombohedral (R3) polymorphs and one cubic (I213) polymorph were identified with increasing pH, corresponding to the T6, T3R3 f and T2 conformations of insulin, respectively. The structure of the cubic T2 polymorph was determined via multi-profile stereochemically restrained Rietveld refinement at 2.7 Å resolution. This constitutes the first cubic insulin structure to be determined from crystals grown in the presence of zinc ions, although no zinc binding was observed. The differences of the polycrystalline variant from other cubic insulin structures, as well as the nature of the pH-driven phase transitions, are discussed in detail.

Structural Evolution of the Pharmaceutical Peptide Octreotide upon Controlled Relative Humidity and Temperature Variation

“…In the framework of assessing the stability of polycrystalline peptide-based pharmaceuticals, XRPD is the most appropriate method in gaining insights into the crystalline integrity of a molecule. This involves the identification of potential polymorphism and the detection of conformational alterations at the unit-cell level (Norrman et al, 2006;Margiolaki & Wright, 2008;Karavassili et al, 2017;Margiolaki, 2019;Spiliopoulou et al, 2020;Triandafillidis et al, 2023). Stability studies aim to establish optimal storage conditions for a drug substance, incorporating tests for thermal stability and, if relevant, sensitivity to moisture.…”

Structural Evolution of the Pharmaceutical Peptide Octreotide upon Controlled Relative Humidity and Temperature Variation

“…In the framework of assessing the stability of polycrystalline peptide-based pharmaceuticals, X-ray Powder Diffraction (XRPD) is the most appropriate method for gaining insights into the crystalline integrity of a molecule. This involves the identification of potential polymorphisms and the detection of conformational alterations at the unit-cell level [9][10][11][12][13][14]. Stability studies aim to establish optimal storage conditions for a drug substance, incorporating tests for thermal stability and, if relevant, sensitivity to moisture.…”