Scoring the Synthesizability of Any Novel Non-natural Amino Acid

Conclusions & Future Directions Our synthesizability tool: Creates multiple protected versions of a given non-natural amino acid Considers SPPS specifical protection groups Scores the synthesizability of each route Facilitates the evaluation of retrosynthesis planning Our tool can be used to: Rank the synthetic feasibility of all the protection strategies for a given novel NNAA In addition to other peptide optimization scoring functionsWe are conducting validation studies on the synthesis and characterization of some of the non-natural amino acids for the KEAP1-NEH2 model system. I. Generate Protected Compounds.A cheminformatics tool was built to obtain multiple protected versions of each NNAA, suitable for SPPS. 3 II.Retrosynthesis scoring.We used our single-step retrosynthesis model (AiZynthFinder 4 ) trained on USPTO data and the stocks for eMolecules 5 .The generated routes were scored by accumulating scores for the reactions in the route and were filtered with the feasibility predicted by a forward Chemformer model 6 .Finally, the routes were scored with a rank score for reaction class based on historical data, referred as the Synthetic Feasibility (SF) score.