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Updated: Jan 21, 2026

Quaternary Structure Modeling Through Chemical Cross-Linking Mass Spectrometry: Extending TX-MS Jupyter Reports
Published on: October 20, 2021
The quaternary structure of insulin glargine and glulisine under formulation conditions
Norbert Nagel1, Melissa A Graewert2, Mimi Gao1
1Sanofi-Aventis Deutschland GmbH, R&D, Industriepark Höchst, 65926 Frankfurt, Germany.
Abstract:
The quaternary structures of insulin glargine and glulisine under formulation conditions and upon dilution using placebo or water were investigated using synchrotron small-angle X-ray scattering. Our results revealed that insulin glulisine in Apidra® is predominantly hexameric in solution with significant fractions of dodecamers and monomers. Upon dilution with placebo, this equilibrium shifts towards monomers. Insulin glargine in Lantus® and Toujeo® is present in a stable hexamer/dimer equilibrium, which is hardly affected by dilution with water down to 1 mg/ml insulin concentration. The results provide exclusive insight into the quaternary structure and thus the association/dissociation properties of the two insulin analogues in marketed formulations.
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