Genetically Encoded Libraries of Nonstandard Peptides
Figure 4
Selection of nonstandard peptides from libraries generated by flexizyme-based genetic code reprogramming. The flexizyme system was used to acylate tRNAs with nonproteinogenic amino acids. The nonstandard peptide libraries were expressed in a reconstituted cell-free translation system in the mRNA display format. (a)Selection of cyclic N-methyl-peptides against E6AP. N-Chloroacetyl-D-tryptophan was reassigned to AUG, and four N-methyl-L-amino acids were independently reassigned to one of the NNU codons. (b)Selection of thioether-cyclized peptides against Akt2. Each enantiomer of N-chloroacetyltyrosine was reassigned to the initiation AUG codon. (c)Selection of cyclic peptides containing N-6-trifluoroacetyl-L lysine against sirtuin 2 (SIRT2). Each enantiomer of N-chloroacetyl-tyrosine was reassigned to the initiation AUG codon and N-6-trifluoroacetyl-L-lysine () was reassigned to the elongation AUG codon.
