Quantitative codon optimisation of DNA libraries encoding sub-random peptides: design and characterisation of a novel library encoding transmembrane domain peptides.
Codons for amino acids sharing similar chemical properties seem to cluster on the genetic codon table. Such a geographical distribution of the codons was exploited to create chemically synthesised DNA that encodes peptide libraries containing only a subset of the 20 natural amino acids. The frequency of each amino acid in the subset was further optimised by quantitatively manipulating the ratio of the four phosphoamidites during chemical synthesis of the libraries. Peptides encoded by such libraries show a reduced complexity and could be enriched in peptides of a desired property, which are thus more suitable when screening for functional peptides. Proof of concept for the codon-biased design of peptide libraries was shown by design, synthesis, and characterisation of a transmembrane peptide library that contains >80% transmembrane peptides, representing a 160-fold enrichment compared with a fully randomised library.
Larsson
Ola
O
Center for Genomics and Bioinformatics (CGB), Karolinska Institutet, 171 77 Stockholm, Sweden.
Thormeyer
Dorit
D
Asinger
Arian
A
Wihlén
Björn
B
Wahlestedt
Claes
C
Liang
Zicai
Z
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D003062:Codon; D015723:Gene Library; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics*; D009841:Oligonucleotides / Q000138:chemical synthesis; D019151:Peptide Library; D010455:Peptides / Q000032:analysis / Q000737:chemistry* / Q000235:genetics*; D017434:Protein Structure, Tertiary
D000596:Amino Acids; D003062:Codon; D008565:Membrane Proteins; D009841:Oligonucleotides; D019151:Peptide Library; D010455:Peptides