(318f) The Role of Water in the Crystallisation and Nucleation of Glycine Homopeptides
AIChE Annual Meeting
2020
2020 Virtual AIChE Annual Meeting
Separations Division
Nucleation and Growth II
Tuesday, November 17, 2020 - 9:15am to 9:30am
Glycine is an important and well-studied amino acid, being abundant in proteins and utilized as a pharmaceutical excipient. Its simple hydrogen side chain makes this an ideal case study candidate for biopharmaceutical research.6 Here we investigate the crystallisation of pure and hydrated forms of mono-, di- and tri-glycine. However, only mono- and tri-glycine are known to crystallise in hydrated forms. The crystallisation of mono, di- and tri-glycine from aqueous solutions was compared in this research. The single crystal structure of triglycine dihydrate (TGDH) form was solved for the first time, which can help us to analysis the interaction between water and peptide molecules. For Glycine homopeptides, crystal forms of up to five glycine residues in a peptide chain are known, and the antiparallel β sheet structure was found is the most stable crystalline form for triglycine anhydrate. However, from the crystal structure of triglycine dihydrate, the backbone of it trends to bend in water to find a more stable form.
The activation free energy (â³Gc) of nucleation was calculated based on induction time measurement at different supersaturation and different temperature. Compare with mono- and di-glycine, triglycine has the greatest decrease in â³Gc at 283.15K when the form is dihydrate. Molecular modelling was also used to investigate the delicate balance of conformation and packing forces, as a function of chain length.
In summary, we solved the first TGDH crystal structure and explored the water role in the hydration conformation of peptides. The modeling work help us to find several competing effects which are driving TGDH. It also gives protein crystallisation a new insight about the interaction between water and protein, this discovery has an important implication for pharmaceutical engineering and biology research.
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