The N-pentenoyl protecting group for aminoacyl-tRNAs

The elaboration of misacylated transfer RNAs by T4 RNA ligase-mediated condensation of an aminoacylated pdCpA derivative and a tRNA (transcript) missing the two 3′-terminal nucleotides requires that the aminoacyl moiety of the dinucleotide be stabilized during the ligation reaction. This can be done conveniently by the use of a simple 4-pentenoyl group attached to Nα of the amino acid. The pentenoyl amide can be deblocked readily with aqueous iodine, presumably via an iodolactone intermediate. This protecting group can be used in conjunction with side chain protecting group for amino acids having side chain functionality, thus permitting the elaboration of proteins bearing side chain protecting groups that can be removed in a subsequent step (e.g., caged proteins). In addition, an aminated analogue of the pentenoyl protecting group, the unnatural amino acid allylglycine, can be employed as part of the peptide backbone to afford a protein cleavable by iodine.