Attempts Towards the Bucky-amino Acid Acylation of the Phospho-cytidine-phospho-adenosine (pdCpA) Subunit

Abstract

The irreversible adsorption of fullerene (C₆₀) substituted amino acids to the hydrophobic resin bead surface during solid phase peptide synthesis leads to low yields. Due to challenge in preparing sufficient C₆₀-substituted phenylalanine (Bucky amino acid, Baa) an alternative route to fullerene-substituted peptides was investigated. The first step is the synthesis of the amino acylated phospho-cytidine-phospho-adenosine subunit (pdCpA-Baa) prior to enzymatically ligating it to a truncated tRNA. However, despite the successful synthesis of the cyanomethyl ester, Fmoc-Baa-OCH₂CN (1) no reaction is observed between the hydrophilic pdCpA and hydrophobic Baa even in the presence of cationic surfactant or in DMF solution. As an alternative method a N,N’-diisopropylcarbodiimide coupling route was investigated, which despite the presence of an appropriate m/z in the MALDI-MS did not lead to an isolable product. The successful coupling of a hydrophobic perfluorophenyl ester (Fmoc-Gly-OPfp) to pdCpA suggest that it is steric bulk rather than miscibility that precludes the Baa coupling.