Custom Oligonucleotides-Small Molecule Conjugation Service

Fig. 1 Biotin.^1,3

Biotin is a heterocyclic compound with C5-carboxylic acid side chain, sulfur ring fused urea group and tetrahydrothiophene group, and its molecular weight is about 244.3032. The highly specific binding of avidin and biotin allows chemically modified versions of biotin to be widely used in protein separation, biochemical analysis, protein detection or targeting systems. Biotin is a relatively small component, so modification or biotinylation of macromolecules does not significantly affect its physical or chemical properties. Biotin can bind to the UTP or dUTP-5' carbon of the nucleic acid molecules and be detected by avidin. Biotin-labeled DNA or oligonucleotide preparation is generally carried out enzymatically or chemically.

Fig. 2 Digoxin.^2,3

Digoxin is one of the oldest drugs in the field of cardiology. Digoxin can selectively bind to the Na⁺-K⁺ ATPase on the myocardial cell membrane and inhibit the activity of the enzyme, resulting in impaired Na⁺-K⁺ active coupling transport inside and outside the cell membrane, thereby affecting the intracellular Na⁺ and Ca²⁺ concentrations. Digoxin increases myocardial contractility, increases stroke volume and decreases heart rate. By forming a coupling construct with oligonucleotides, specific drug delivery can be accomplished or the detection of digoxin can be realized by the principle of base pairing.

Glycosylation is a reaction process in which glycans are linked with hydroxyl groups or other functional groups of glycosyl acceptors to form glycoconjugates. Glycan-modified lipids and proteins are involved in molecular interactions in nearly all areas of life. GlycoRNAs, which are assembled by classical N-glycan biosynthesis machinery and form sialic acid- and fucose-rich structures, are first demonstrated to be present in multiple cell types in 2021, making RNA a major target of glycosylation from then on.

Fig. 3 Glycosylation takes place on the cell surface.

Aptamers generally refer to single-stranded DNA/RNA small molecules of 20-100 nucleotides in length. Aptamers are able to form many secondary structures through base-pairing interactions and confer specific tertiary structures to aptamers through the combination of secondary structures. Aptamers have strong binding ability and recognition ability, they can distinguish conformation isomers, and show tight binding to the target. Since aptamers are usually designed based on nucleic acid structure, they can be directly synthesized instead of cellular expression and extraction. Depending on the design and drug loading status, aptamers can be designed as antagonists, agonists or RNA decoy aptamers. ApDCs can be used as detection tools and can also be applied in fields such as drug delivery.

DEL is a technique widely used in medicinal chemistry for the synthesis and screening of extremely large collections of small molecule compounds. As a bridge between combinatorial chemistry and molecular biology, DEL can accelerate the drug discovery process, providing data for target validation and hit identification. The core of DEL technology is to combine specific compounds or building blocks with DNA fragments and use them as identification barcodes to guide and control the chemical synthesis process. Synthesized conjugates can enable large-scale creation and querying of libraries through affinity selection. The synthetic routes for DEL developed so far can be divided into two approaches, namely solid-phase and liquid-phase synthesis. Solid-phase synthesis can satisfy most chemical reactions, while solution-phase synthesis is limited by the solubility of oligonucleotides.

Fig. 4 The basic process of DEL screening.