The elimination of side-chain orthogonal protective groups of arginine and histidine is critical to improve solid phase peptide synthesis (SPPS) sustainability through an increase in the peptide atom economy (AE) and decrease in impurities generated during the final cleavage step. The combination of Oxyma Pure and tertbutyl ethyl carbodiimide (TBEC) in the correct ratio allowed the use of side-chain free arginine and histidine in green solvents. Etelcalcetide and vasopressin intermediates as well as critical key fragments of liraglutide and semaglutide were successfully synthetized via SPPS using optimized conditions. In addition, the Oxyma Pure/TBEC protocol in NBP/DMC was successfully applied to a sequence containing side-chain unprotected arginine, histidine, tryptophan and tyrosine.Oxyma Pure/TBEC coupling protocol in green solid phase peptide synthesis (GSPPS) eliminates protective groups on Arg and His, enhancing atom economy and reducing impurities during cleavage. The technology was extended to side-chain-free Tyr and Trp.

Fantoni, T., Orlandin, A., Di Stefano, I., Macis, M., Tolomelli, A., Ricci, A., et al. (2024). Solid phase peptide synthesis using side-chain unprotected arginine and histidine with Oxyma Pure/TBEC in green solvents. GREEN CHEMISTRY, 26(21), 10929-10939 [10.1039/d4gc03209h].

Solid phase peptide synthesis using side-chain unprotected arginine and histidine with Oxyma Pure/TBEC in green solvents

Fantoni T.;Di Stefano I.;Tolomelli A.;Cabri W.;Ferrazzano L.
2024

Abstract

The elimination of side-chain orthogonal protective groups of arginine and histidine is critical to improve solid phase peptide synthesis (SPPS) sustainability through an increase in the peptide atom economy (AE) and decrease in impurities generated during the final cleavage step. The combination of Oxyma Pure and tertbutyl ethyl carbodiimide (TBEC) in the correct ratio allowed the use of side-chain free arginine and histidine in green solvents. Etelcalcetide and vasopressin intermediates as well as critical key fragments of liraglutide and semaglutide were successfully synthetized via SPPS using optimized conditions. In addition, the Oxyma Pure/TBEC protocol in NBP/DMC was successfully applied to a sequence containing side-chain unprotected arginine, histidine, tryptophan and tyrosine.Oxyma Pure/TBEC coupling protocol in green solid phase peptide synthesis (GSPPS) eliminates protective groups on Arg and His, enhancing atom economy and reducing impurities during cleavage. The technology was extended to side-chain-free Tyr and Trp.
2024
Fantoni, T., Orlandin, A., Di Stefano, I., Macis, M., Tolomelli, A., Ricci, A., et al. (2024). Solid phase peptide synthesis using side-chain unprotected arginine and histidine with Oxyma Pure/TBEC in green solvents. GREEN CHEMISTRY, 26(21), 10929-10939 [10.1039/d4gc03209h].
Fantoni, T.; Orlandin, A.; Di Stefano, I.; Macis, M.; Tolomelli, A.; Ricci, A.; Cabri, W.; Ferrazzano, L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/999847
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