A multidisciplinary team led by Lenka Žáková, Jakub Kaminský, and Jiří Jiráček, from IOCB Prague studied short fragments of preptin. Preptin is a 34-amino-acid-long peptide hormone secreted from pancreatic beta-cells and is supposed to have a role in insulin secretion and bone metabolism.
Scientists aimed to determine if the C-terminal octa- and nonapeptide fragments of human preptin can retain their biological activity and how the introduction of stabilizing motifs into their structures can affect their activities.
They reported the design, in silico modelling, synthesis, and structure-activity relationship of six truncated analogs of human preptin. They also studied how the secondary structure of preptin fragments can affect their ability to stimulate the release of intracellular calcium ions. A nonapeptide analog stabilized in the cis conformation by a staple prepared by olefin metathesis stimulated release of calcium ions similarly as the full-length human preptin.
The results of the research could bring new possibilities for the design of new drugs for the treatment of diabetes and osteoporosis.
Read the paper:
- Lubos, M.; Mrázková, L.; Gwozdiaková, P.; Pícha, J.; Budešínský, M.; Jiráček, J.; Kaminský, J.; Žáková, L. Functional stapled fragments of human preptin of minimized length. Org. Biomol. Chem. 2022. https://doi.org/10.1039/D1OB02193A
