Introduction of PICT
Invented in Zonsen Biotech, the essence of PICT (Peptide Information Compression Technology) is to make efficient use of the biochemical property of cyclic peptides so that one cyclic peptide could contain the amino acid sequence information of very large number of peptides. As a result, a library with about 80,000 cyclic 80-mer peptide compounds will contain about 500,000,000 different peptide sequence information.
Concept of complete peptide library
A complete peptide library refers to a collection of peptides which embodies all possible natural amino acid sequences based on the peptide size. For example, all possible different tripeptides include 203 = 8000 peptides, while all possible different tetrapeptides include 204 = 16,000 peptides, thus a complete tripeptide library must have 8000 distinctive peptides and a complete tetrapeptide library must have 16, 000 distinctive peptides.
Information compression efficiency of PICT
As shown below, a linear tripeptide with 3 different amino acids contains 2 different dipeptides, while a cyclic tripeptide contains 3 different dipeptides. Based on this principle, using 70-mer cyclic peptide as example, we can design a 70-mer cyclic peptide which will include 70 different dipeptides, 70 different tripeptides, 70 different tetrapeptides, and so on and so forth, all the way up to 70 different 70-mer peptides. The result is one 70-mer cyclic peptide could contain amino acid sequence information of 4830 different peptides. In another word, a 70-mer cyclic peptide library constructed in this way renders an amazing compression ratio of 4830 for the embedded amino acid sequence information. For an 80-mer cyclic peptide, the compression efficiency will be even higher.
Illustration of peptide library construction process
Comparison to other technologies
PICT peptide library has the following advantages when compared to a traditional chemically synthesized peptide library:
- A lot more peptide sequence information.
- More variety of peptide compound series and sizes, which will certainly increase the hit rate in the screening process.
- Far less cost and time to build up.
- Much easier and cheaper to regenerate.
Phage display is another popular technology to make peptide libraries. Although the capacity of these libraries is generally huge, the nature as compound mixtures is troublesome. We think PICT peptide library at least exhibits these outstanding features when compared to this kind of mixture libraries:
- Each peptide is individually expressed, purified, quantified and QC verified.
- Compound stability is higher because of the peptide-bond cyclic structure.
- Library is intrinsically complete due to the design strategy.
- Peptides are packaged in 96-well HTS format for the convenience of the subsequent screening.
- Rebuilding the entire library is easy and cheap.
- Biological assay methods for hit screening are not limited to affinity/binding assays. Cell-based functional assays, even in vivo assays can be chosen as well.
- There is no interference between compounds during the screening process.
- False positive or false negative rate during the hit screening is lower.