<br/>Amongst the biologic drugs family, peptides, as polymers of amino acids, play important roles in human physiology and are hence an important class of therapeutics. The unique selling point of peptides is that they are selective, which translates into them being efficacious, safe and tolerable for administration to humans. The economic bottleneck of peptide manufacture, analogous to many biomolecules, is the challenges associated with purification as chromatographic methods are most widely used. However, advances in crystallisation optimisation methods has resulted in this technique being a genuine alternative to chromatography for peptide purification.<br/>Here we present the nucleation kinetics, derived from induction time data, of a homologous series of mono-, di- and tri-glycine. The induction time is found to increase with increasing chain length of the peptide. However, the increase in the induction time between di- and tri-glycine is found to be much lower than between mono- and di-glycine. This is found to be due to the preferential nucleation of a tri-glycine di-hydrate structure, rather than pure tri-glycine. A single crystal of this form was isolated, where the coordinates of the crystal structure are solved for the first time.<br/>Molecular modelling examines the energetically favourable molecular conformation and intermolecular solute/solute and solute/solvent interactions, to further uncover the molecular mechanisms behind the experimental observations. In particular, the crystallisation of the tri-glycine hydrate is examined, with respect to why of the three molecules only the tri-glycine presents a hydrated structure.<br/>This study uncovers detailed molecular chemistry, which underpins the nucleation of peptides of different chain lengths, providing insight into how the self-assembly mechanism changes from amino acid, to peptide to protein. This information is fundamental to maturing crystallisation as a viable peptide and protein purification technique.

Crystallization of peptides: Case of glycine homopeptides

ACS Fall 2020 Virtual Meeting

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