Sristi Raj Rai, Amity University Kolkata
Nucleic acid (DNA or RNA), the biopolymeric backbone to all life forms encodes for all biological information crucial for metabolic activities. Therapeutic targeting of these molecules along with peptides is highly in fashion, and the method ranges from small drug molecules to macromolecules (>100KDa) such as CRISPR-Cas. These molecules have been chosen strategically, as their functionality/non-functionality decides the presence/absence of various pathologies in one’s body. Being the hub for mutations and residing non-coding RNAs (ncRNA) that has the capability to regulate gene expression at the transcriptional and post-transcriptional levels; needs to be monitored closely. CRISPR-Cas, along with antisense oligonucleotides (ASOs) bears the power to restore these genetic abnormalities. Therefore, constructions of biohybrid abiotic polymers that can target nucleic acid in combination with peptides have been constructed in the past few years. Where on one end, it can easily expose its amino acids capable of interacting with diverse biological species, and on the other end, the nucleobases via base-pairing interact with other nucleic acids.
Numerous groups have studied the functionality of the material in diverse ways, despite that there is a lack of high-throughput selection/decoding procedures for mixed peptide biohybrids. Therefore, Sebastian Pomplun and his group implemented synthetic combinatorial chemistry and tandem mass spectrometry (MS/MS) sequencing for these biohybrids, giving rise to 100 million-membered assembled combinatorial library which can help in designing novel compound. Thus, has opened a new area for the chemistry of the compounds to be compared and analyzed. Their designed compounds favored binding with oligonucleotides with high specificity and affinity. Moreover, they were able to scan the libraries and identified a selective nanomolar binder to RNA hairpins over DNA by Affinity Selection-Mass Spectrometry (AS-MS – a tag-free approach). Hence, guarantees a scheme that can target specific oligonucleotide strands. In the coming future, they will be focusing their experiments on non-biological sources, thereby creating a new possible window for other possible reactions.
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SOURCE – Sebastian Pomplun, Zachary P. Gates, Genwei Zhang, Anthony J. Quartararo, and Bradley L. Pentelute, Journal of the American Chemical Society Article ASAP. DOI: http://10.1021/jacs.0c08964
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