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Unnatural amino acids (residues that do not exist in normal proteins) can be inserted into proteins for detailed mechanism analysis if they are escorted to the ribosome by the orthogonal inhibition tRNA of the identified termination codon. CD BioSciences has accumulated rich experience in peptide research. Using its peptide discovery platform based on mRNA display technology, it can build a peptide library containing a variety of unnatural amino acids for ligand screening, diagnosis and treatment.
Unnatural amino acids (UAAs), that is, naturally occurring or chemically synthesized non protein amino acids, are becoming more and more important as a tool for modern drug discovery and research. Because of their infinite structural diversity and functional diversity, they are widely used as chiral building blocks and molecular scaffolds for constructing combinatorial libraries. When they are combined into therapeutic peptide mimics, they are powerful tools for drug discovery. As molecular probes, they help to better understand the functions of biological systems. Peptides have gradually become peptide candidates because of their improved stability in vivo, enhanced efficacy, better oral absorption and improved bioavailability. In the development of peptide mimics, unnatural amino acids can be used to change the tertiary structure of peptides and modify side chains, making the design of candidate drugs perfectly match their biological targets.
Fig. 1 Scheme for insertion of unnatural amino acids into mRNA display libraries via amber suppression. (Li, et al., 2002)
The introduction of unnatural amino acids is one of the key points for the successful discovery of drugs. Because mRNA display strategy is more advantageous than synthetic peptide library, it has large library size and potential for directional evolution. A four base codon strategy has been found to bind a variety of unnatural amino acids to specific locations of proteins. The constructed peptide library contains multiple unnatural amino acids from mRNA, which contains three four base codons AGGU, CGGU and GGGU at a single randomly selected location. mRNA may also contain amber codons at random positions in the (NNK)n sequence. The construction of unnatural peptide libraries by four base codon mediated mRNA display provides a widely applicable and highly flexible method for searching for effective peptide ligands and drugs.
Based on mRNA display technology, CD BioSciences can provide global customers with the construction of unnatural peptide libraries to support global customers in basic research and drug discovery. In the construction of unnatural peptide library, we extended the mRNA display method to include a variety of unnatural amino acids by introducing three different four base codons into a single randomly selected position on mRNA. In addition, another unnatural amino acid can be introduced by suppressing the amber codon in the (NNK)n nucleotide sequence that may appear on mRNA.
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CD BioSciences has many years of project development experience in peptide discovery. Based on the mRNA display technology platform, it can provide customers with various peptide library construction services. If you are interested in our services, please contact us for more details.
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