Design and Synthesis of New Acid Cleavable Linkers for DNA Sequencing by Synthesis

Abstract

A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2'-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by 1H-NMR, 31P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions.

Light in Gold Catalysis

“…This chain mechanism was consistent with the value 6.6 as the quantum yield for this process. It can be assumed that the oxidation of gold(II) (226) to gold(III) (227) was just mainly accomplished by the aryldiazonium salt and that the radical chain from time to time needed to be reinitiated by regeneration of the photosensitizer (gray, added by the authors of this review).…”

“…After demonstrating the feasibility of an energy transfer reaction by using the dinuclear gold­(I) catalyst, the Hashmi group exploited this promising technique further and disclosed a C­(sp 3 )–H acetalization of saturated heterocycles ( 367 ) (Scheme ). Acetals derived from cyclic ethers are highly applicable motifs , and can be found in several drugs (e.g., epirubicin, streptomycin). Herein, diverse alcohols for the acetalization of ethers were examined and further expanded to thioethers and amides.…”

Chiral Diaryliodonium Phosphate Enables Light Driven Diastereoselective α-C(sp3)–H Acetalization

“…While trapping of the cationic species by external nucleophiles can lead to undesired termination of the polymerization, it can be employed to functionalize heterocyclic C(sp 3 )−H bonds. Encouraged by diverse applications of the 2,5-disubstituted tetrahydrofuryl acetals in drug discovery, 10 liquid crystal display devices, 11 and DNA-sequencing, 12 we targeted asymmetric α -C(sp 3 )−H acetalization of readily accessible chiral tetrahydrofurans through oxidative coupling with alcohols (Scheme 1). We envisioned that the outlined strategy would provide a new avenue in the stereochemical control of exocyclic acetals ( trans versus cis ).…”

Visible Light-Induced α-C(sp3)–H Acetalization of Saturated Heterocycles Catalyzed by a Dimeric Gold Complex

“…Several drugs that contain this motif are applied to treat diseases (Figure ). There are also other applications based on structures containing this motif, such as liquid crystal display devices and DNA sequencing . In addition, hydroxyl groups can be protected as tetrahydrofuranyl ethers in multistep organic syntheses as well as in peptide, nucleotide, carbohydrate, terpenoid, and steroid chemistry .…”

“…There are also other applications based on structures containing this motif, such as liquid crystal display devices 7 and DNA sequencing. 8 In addition, hydroxyl groups can be protected as tetrahydrofuranyl ethers in multistep organic syntheses as well as in peptide, nucleotide, carbohydrate, terpenoid, and steroid chemistry. 9 There are different strategies for the preparation of cyclic ether acetals; 10 the most direct way uses THF in the presence of single-electron oxidants via radical pathways.…”