?-Sheet Induced Helical Self-Assembly Structure Formation by Dityrosine Dipeptide: Crystallographic Evidence and Other Biophysical Studies

Self-assembled structures derived from short peptides are a versatile class of organic building blocks which have shown great potential in a wide range of domains. In the current study, side-chain protected dityrosine based short peptide (TP) was synthesized, and its conformation accompanied by a self -assembly pattern was investigated through several spectroscopic studies and single crystal X-ray analysis. The single crystal X-ray analysis of TP confirmed that it exhibited a B-sheet pattern which further self-assembled to form B-sheet-promoted helical architec-tures by various noncovalent interactions. To the best of our knowledge, this is the first crystallographic report of a side-chain protected dityrosine based short peptide adopting B-sheet -promoted helical structures. Morphological analysis of TP also revealed B-sheet as well as helical conformations. NMR study suggested that both amide hydrogens of TP are involved in intermolecular hydrogen bonding. Moreover, CD spectroscopy established the self-assembly phenomenon of TP in the solution state by showing both corresponding B-sheet and alpha-helix bands. Hirshfeld surface analysis and DFT study also concluded similar results. These kinds of small peptide units mimicking important protein secondary structures like helical assembly would be of pivotal significance as they may act as small peptidomimetics, mimicking the protein Hotspot area.

Automated summary

Self-assembled structures derived from short peptides, like the dityrosine-based short peptide (TP) studied in this research, have great potential in various domains. Through spectroscopic studies and single crystal X-ray analysis, it was confirmed that TP adopted a B-sheet pattern and further self-assembled into B-sheet-promoted helical architectures. This is the first crystallographic report of this kind of short peptide adopting B-sheet-promoted helical structures. CD spectroscopy, NMR study, and other analyses also supported the self-assembly phenomenon of TP. These small peptide units mimicking protein secondary structures could be of pivotal significance.