Abstract
Native Chemical Ligation (NCL) is a powerful method for peptide synthesis. Originally, NCL occurs between C-terminal thioester and N-terminal cysteine. In this thesis, the thiol containing auxiliaries were assembled at the side-chain of aspartic acid (Asp). The thiol protected Asps were used as a building block to synthesize tripeptides H-AA1-Asp(RSH)-Glu-OH (AA1 = Gly, Val, Ser, Asp, His) which were then reacted with thioester, Cbz-AA2-SPh (AA2 = Gly, Ser, Phe, Leu, Pro, His), by NCL. Photo-irradiation was applied to remove the auxiliaries after ligation to afford tetrapeptides Cbz-AA2-AA1-Asp-Glu-OH. The results showed that the thiol containing auxiliary at Asp can assist the amide bond formation by NCL with moderate to good yields, except that the N-terminal amino acid of tripeptides was valine due to steric hindrance. However, when a serine next by Asp (at either N- or C-terminal), uncharacterized side-product was obtained after photo-irradiation.