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Analysis of Glulisine Crystallisation Utilising Phase Diagrams and Nucleants

1
Biomolecular Medicine, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK
2
Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK
3
Queen’s Medical Centre, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2HA, UK
*
Author to whom correspondence should be addressed.
Crystals 2019, 9(9), 462; https://doi.org/10.3390/cryst9090462
Received: 1 August 2019 / Revised: 29 August 2019 / Accepted: 1 September 2019 / Published: 3 September 2019
(This article belongs to the Special Issue Novel Strategies for Improved Protein Crystallization)
Glulisine is a US Food and Drug Administration (FDA) approved insulin analogue, used for controlling hyperglycaemia in patients with diabetes mellitus (DM). It is fast acting which better approximates physiological insulin secretion, improving patient outcome. Crystallisation of Glulisine was analysed by its crystallisation phase diagram and nucleation-inducing materials. Both the hanging drop vapour diffusion and microbatch-under-oil methods were used and compared. We have shown that the same protein can have different solubility behaviours depending on the nature of the salt in the precipitating agent. In the case of Glulisine with magnesium formate, lowering the precipitant concentration drove the system further into supersaturation resulting in the formation of crystals and precipitation. This was the opposite effect to the usual scenario where raising the precipitant concentration leads to supersaturation. Glulisine with sodium potassium tartrate tetrahydrate (NaKT) followed the expected trend of forming crystals or precipitate at higher concentrations and clear drops at lower concentrations of the precipitant. The outcomes of crystallisation using the different crystallisation methods is also described. Glulisine was successfully crystallised and the crystals diffracted up to a resolution limit of 1.4 Å. View Full-Text
Keywords: proteins; macromolecules; crystals; crystallization; nucleation; phase diagram; insulin; Glulisine proteins; macromolecules; crystals; crystallization; nucleation; phase diagram; insulin; Glulisine
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Li, Y.; Govada, L.; Solomon, H.V.; Gillis, R.B.; Adams, G.G.; Chayen, N.E. Analysis of Glulisine Crystallisation Utilising Phase Diagrams and Nucleants. Crystals 2019, 9, 462.

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