DNA-encoded libraries (DELs) technology is one of the most cutting-edge technologies in the field of new drug discovery. In a DELs, each compound is tagged with a known and unique DNA barcode. A specific nucleic acid sequence encodes each building block of a compound library, and the compound library is synthesized by combining a "split and pool" strategy with combinatorial chemistry to synthesize millions of compounds.
Therefore, DNA sequences comprise the core of the technology for constructing DELs, which are interpreted in groups of three nucleotide bases, known as codewords or codons. The codon records information about the building blocks and, together with primers, can be used for PCR amplification. After high-throughput sequencing and decoding the DNA codon information, identifying the structure of enriched protein binders after DELs selection.
Alfa Chemistry is a quality provider of DELs technology with extensive experience in the field. We provide DNA codon design services, with the ability to design according to the connection mode and the dimensions of DELs.
Design Methods
The design methods of DNA codon sequences can theoretically be divided into positive design and negative design.
- Positive design methods require optimizing affinity to fully hybridize matching sequences, including Tm value (the melting temperature of an oligonucleotide duplex) constraints, GC-content constraints, energy minimization constraints, etc.
- Negative design methods require optimizing sequence specificity, including Hamming distance constraints, sequence minimum symmetry constraints, minimum free energy constraints, etc.
A good codon design should embody both high affinity and high specificity, and kinetic factors should also be considered. The optimal combination of these constraints is a better way to solve codon sequence problems.
Design Principles
DNA sequences can form loops or other complex structures through base pairing. ACGT is an acronym for the four types of bases found in a DNA molecule: adenine (A), cytosine (C), guanine (G), and thymine (T). In a Watson-Crick base pairing, A is complementary with T while C is complementary with G, which is a relatively strong connection. There are two hydrogen bonds between AT and three hydrogen bonds between GC. Besides, in order to ensure the stability of the double strand after hybridization, the GC content is usually required to be higher than a certain value. In summary, the DNA codon sequence design services provided by Alfa Chemistry follow the principles listed below.
- Determine the appropriate GC content (composition).
- Ensure the balance of ATCG bases.
- Avoid the presence of complementary sequences, which can lead to hairpin structures formed by single-stranded DNA molecules folding back on themselves.
- Control the number of identical consecutive bases and repeating base pairs.
- Ensure the Hamming distance of each pair of codon sequences to distinguish different codons.
Choose Us
- Professional team: Our team is composed of highly educated masters and doctors and has many years of experience in DNA codon design.
- Advanced platform: We constantly update and improve our capabilities to provide accurate and reliable services.
- Competitive price: We provide DNA codon design services at a competitive price when compared to our peers.
- One-stop services: We provide custom design method development and technical support for the whole process according to customer's requirements.
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