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Development of oligonucleotide based probes for specific and sequence-unrestricted targeting
of double-stranded DNA (dsDNA) is a long-standing goal of biological chemistry and
molecular biology due to their prospect as molecular tools that can detect, regulate and modify
genes. Development of triplex forming oligonucleotides (TFOs), peptide nucleic acids (PNAs)
and minor groove binding polyamides have resulted in significant progress toward this
direction. However, their inherent limitations leave an urgent need for alternative strategies
capable of sequence-unrestricted targeting of double-stranded DNA (dsDNA). Dr. Hrdlicka
and coworkers have developed a novel approach for targeting of dsDNA, called “Invader
approach,” which has made a significant progress towards these shortcomings. This approach
was originally explored using N2'-pyrene-functionalized-2'-amino-α-L-LNA (locked nucleic
acid) as the key components. However, synthetic challenges and commercial inaccessibility
impeded full characterization of DNA-targeting applications based on these monomers.
Therefore, access to simple and more readily accessible mimics of these building blocks is
highly desired.
In the first part of my talk will briefly summarize my graduate research work on the discovery
of novel building blocks for the Invader-mediated recognition of mixed-sequence DNA
hairpins and chromosomal DNA under non-denaturing conditions1
(from University of Idaho,
USA). In the second part of my talk I will focus on the development of novel organic catalysts
for the removal of formaldehyde adducts and cross links from FFPE tissue sample2
(from my
Postdoctoral Research work at Stanford University, USA). In the third part, I will briefly
summarize our recent research and development on GalNAc-conjugated oligonucleotides for
the efficient delivery into the liver hepatocytes for the treatment of liver diseases3
(from
Translate Bio, MA, USA).
References:
1. a) Karmakar et al. Org. Biomol. Chem. 2017, 15, 9760-9774, and b) US WO 2012-47442.
2. a) Karmakar et al. Nat. Chem. 2015, 7, 752-758, and b) US WO 2016-044313A1.
3. Karmakar et al. US patent application, 2017 (PTC/US2017/041469). |