The applications of synthetic oligonucleotide analogues are virtually limitless and include numerous biological and material-science uses. Despite this fact, these analogues are expensive to produce in scale and involve complicated synthetic and purification steps. The noted success of peptide nucleic acids (PNAs) further establishes the importance of producing oligonucleotide analogues in an efficient, inexpensive and hassle-free manner. Application of thiol-X ‘Click’ chemistries (e.g. thiol-ene and thiol-Michael reactions) in oligonucleotide synthesis offers an attractive choice to achieve these goals because of its simplicity, robustness, atom economical features and high yields. Using thiol-based click reactions, we developed a new type of thio-ether linked oligonucleotide analogues (Figure 1) termed as ‘Clickable Nucleic Acids’ (CNAs) that exhibit strong hybridizing capacity with complementary targets in a sequence specific manner. As our synthetic protocol relies on one-step polymerizations, it is particularly convenient to synthesize short repeat-sequence oligomers, preparation of those require many steps by conventional step-by-step synthesis. Employment of suitably functionalized monomers can conceive complicated sequences in minimum steps and opens up avenues for sequence-controlled polymer synthesis. The oligomers are non-toxic, stable in biological milieu and can be taken by cells with suitable modification. The CNAs have been successfully used for surface modification and hydrogel synthesis.

Thiol-X reactions in action: Making oligonucleotide analogs in a click

249th National Meeting (2015)

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