CDIS V1.0: A program for non-targeted rapid identification of cyclic dipeptides

Cyclic dipeptides are six-membered cyclic compounds formed through the condensation of two amino acids in a head-to-tail arrangement configuration, exhibiting a wide range of pharmacological activities, such as anticancer, anti-angiogenesis, and neuroprotective effects. The manual identification of cyclic dipeptides requires specialized expertise and is both time-consuming and labor-intensive. To address this challenge, we developed a rapid identification program for cyclic dipeptides, termed the Cyclic Dipeptide Identification System V1.0 (CDIS V1.0), which is based on their fragmentation patterns to enhance identification efficiency. The program integrates mass spectrometry analysis with Python programming, enabling the rapid identification of cyclic dipeptides by screening for characteristic fragment ions and matching diagnostic ions from 24 amino acids using multi-level screening and matching algorithms. Utilizing this program, we identified 13, 45, and 50 natural cyclic dipeptides in the raw and vinegar-processed deer antler, as well as in the vinegar, respectively. Notably, among these were 18 new natural cyclic dipeptides, including the first reported occurrence of five lysine-containing natural cyclic dipeptides. The differences in cyclic dipeptide composition between raw and vinegar-processed deer antler offer significant evidence for the efficacy-modulating effects of vinegar processing on Chinese herbal medicines. The developed program exhibits notable advantages with its intuitive and user-friendly interface, allowing for rapid identification of cyclic dipeptides within seconds and aiding in the discovery of novel cyclic dipeptides not previously documented. The code for CDIS V1.0 is available on GitHub: https://github.com/HRR12308/Cyclic-Dipeptide-Identification-System-V1.0.