From short to medium bioactive Peptide Size: new insights into crystallization and structure determination

Bioactive peptides (BPs)—short amino acid sequences with high selectivity, biocompatibility, and low toxicity—are increasingly important in therapeutics, nutrition, and biotechnology. Despite more than 80 peptide drugs in use and a rapidly expanding global market, development remains limited by poor stability, low oral bioavailability, and challenges in purification. Traditional chromatographic separation is effective but resource-intensive, whereas crystallization offers a sustainable, scalable alternative capable of producing highly pure materials with controlled physical properties. However, peptide crystallization is hindered by molecular flexibility and low crystallization propensity. Advances in soft and hard templating, combined with innovative experimental and computational crystallography, present promising solutions. Structural elucidation via SCXRD and PXRD—enhanced by synchrotron radiation—and tailored phasing strategies are essential for resolving complex peptide architectures. This proposal unites the complementary expertise of Imperial College London (Royal Society-UK)  and Institute of Crystallography (CNR-IT), integrating peptide synthesis, crystallization technologies, and advanced X-ray methodologies to enable efficient, sustainable BP purification and structural characterization.