Facile Synthesis of Non‐Proteinogenic Sulfur‐Containing Cyclic Dipeptides and Their Structure–Antioxidant Activity Relationship
Year: 2025
Type: article
Abstract: Cyclic peptides are peptidic macrocycles with ring-constrained backbones that have distinct physicochemical and biological properties, with the simplest being cyclic dipeptides. Four cyclic dipeptides, cyclo(Pro-Pro), cyclo(Pip-Pip), cyclo(PrS-PrS), and the unique sulfur-rich cyclo(PipS-PipS), were synthesized from unprotected amino acids by using a one-pot thionyl chloride-mediated cyclization process, producing 19%-40% without the use of protective-group strategies. FTIR, NMR, and high-resolution mass spectrometry (HRMS) were used to confirm the structures. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was used to assess antioxidant activity, and it was discovered that sulfur incorporation and six-membered ring size significantly increase radical quenching. A cloud-based platform was used to predict electronic properties, such as HOMO-LUMO gaps, dipole moments, and oxidation potential. Compounds with smaller HOMO-LUMO gaps and lower oxidation potentials had higher DPPH scavenging efficiencies, establishing a clear structure-property-activity relationship. This study identifies promising sulfur-containing cyclic dipeptides for future development as antioxidant therapeutics and presents a scalable pathway to diverse cyclic dipeptides.
Source: Chemistry - An Asian Journal
Authors: Vijay M, Jugun Prakash Chinta
Institution: National Institute of Technology Warangal
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4417180222