Oligomerization of Pharmaceutically Relevant Insulin Analogues for Varying Concentration and Salinity Revealed by Small-Angle X-ray Scattering
Research output: Contribution to journal › Journal article › Research › peer-review
Two different insulin analogues, insulin degludec and lithocholyl insulin, were studied by small-angle X-ray scattering with respect to their self-assembly and interactions in solution at different concentrations of insulin and salt, NaCl. Very different behavior was observed for the two. Insulin degludec, linked to a hexadecanedioic acid, consistently formed di-hexamers, without any further oligomeric growth upon screening of electrostatic repulsions, indicating a stable di-hexamer unit without further oligomerization, as expected in the presence of phenol. The other insulin analogue, linked to the sterol lithocholic acid, formed n-hexamers with n ranging from 1 to 15, increasing with NaCl concentration and insulin concentration, indicating attractive forces in competition with the electrostatic repulsion and solution entropy. At the highest concentration of insulin and NaCl, a liquid crystal phase was observed, which has not previously been identified, featuring a quadratic structure organized into layers, which might hold interesting properties for pharmaceutical applications.
Original language | English |
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Journal | Molecular Pharmaceutics |
Volume | 18 |
Issue number | 9 |
Pages (from-to) | 3272-3280 |
Number of pages | 9 |
ISSN | 1543-8384 |
DOIs | |
Publication status | Published - 6 Sep 2021 |
- insulin degludec, lithocholyl insulin, SAXS, self-assembly, oligomerization, NEUTRON-SCATTERING, MECHANISM, STABILIZATION, PROTRACTION, DEGLUDEC
Research areas
ID: 280664929