Optimized Fmoc solid-phase synthesis of Thymosin alpha1 by side-chain anchoring onto a PEG resin.
Thymosin alpha1 is a 28-amino acid acetylated peptide used for the treatment of hepatitis B and C. This peptide has a difficult sequence because of the presence of consecutive beta-branched amino acids and shows a tendency to form beta-sheet structures, partly as a result of the many protecting groups required to assemble the peptide (up to 20 side-chain protecting groups). Consequently, its synthesis has been generally achieved by convergent solution chemistry. Here we report a straightforward stepwise solid-phase synthesis on a polyethylene glycol solid-support that enables the scaling-up of this key therapeutic peptide.
García-Ramos
Yésica
Y
Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028-Barcelona, Spain.
Giraud
Matthieu
M
Tulla-Puche
Judit
J
Albericio
Fernando
F
D000107:Acetylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry*; D017433:Protein Structure, Secondary; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D013947:Thymosin; D000077596:Thymalfasin