PolyQuant and Fraunhofer IZI develop new codonprecise peptide library
PolyQuant GmbH and Fraunhofer Institute for Cell Therapy and Immunology IZI have developed an advanced new peptide phage display library design.
The 16mer phage display peptide library was synthesized with the help of PolyQuant’s proprietary “codon-precision” technology. The resulting libraries are based on randomly combined sets of codons instead of individually randomized nucleotides. The significant advantage of this approach is that only desired amino acids are present, i. e. such a library does not contain any undesired or stop codons. Moreover, the desired amino acids are present in uniform distribution. The library has a much better coverage of sequence variants than a single nucleotide randomized library where some amino acids are unavoidably overrepresented. The new 16mer 109 codon-precision peptide phage display library is therefore equivalent to an approximately thousandfold larger conventional library.
Fraunhofer IZI has been complementing with a carefully designed core sequence to contain crucial residues at strategic positions, which results in further reduction of the library’s divergence, and an innovative phagemid vector design. Rigorous controls have validated the high quality of the library technology. Based on over 500 000 sequences obtained by Next Generation Sequencing, the majority of the sequences were confirmed to be correct. In addition a special phagemid vector design has been used that obviously prevented emergence of single dominating sequences in the original library as well as in the initial selection rounds.
The Fraunhofer IZI has confirmed the advantages of the codon-precision synthesis approach in combination with innovative vector design in projects with several different targets. Studying the results achieved, Dr. Szardenings commented: “After 18 years with peptide phage display this is for me the first library generating in 2 selection rounds on a single antibody exclusively binding clones without a single clone being amplified. This means all have reasonable affinities and I have a plethora of binding motif variants! This is only possible with an extremely balanced library DNA generated by PolyQuant’s codon-precise synthesis”.
The development of the combinatorial library technology is funded by the Federal Ministry of Economy and Technology, according to the decision of the German Bundestag.
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