Reactions

Letters to the editor

Photopharmacology and receptor reprogramming

A recent C&EN article related to the emerging field of photopharmacology, “Lighting the Way to More Targeted Treatments” (April 2, page 25), inspires a further obvious step, ligand-based receptor reprogramming. This would allow for the development of new sensory capabilities. These capabilities, including an ability to directly detect harmful radiation (ultraviolet and even X-ray) via the reprogramming of temperature-sensing transient receptor potential vanilloid (TRPV) skin receptors, could be a very useful tool in our technology-rich environment.

The feasibility of this approach has already been demonstrated by providing light-sensing capabilities to adenosine receptors in our recent publication (Bioconjugate Chem. 2014, DOI: 10.1021/bc5003373). While this research is in the very early stages of development, it has all the required characteristics of transformative technology.

Andrei A. Gakh
Bethesda, Md.

DNA i-motifs

I was excited to see that the field of alternative and multistranded DNA molecules is continuing to grow at such a fast pace, with the discovery of yet another type of quadruplex DNA in the human genome—that is, intercalated motifs (i-motifs) (Nat. Chem. 2018, DOI: 10.1038/s41557-018-0046-3). The article “Folded DNA Structures Found in Human Cells” (April 30, page 8) discusses yet another significant scientific moment in the evolution of structural polymorphisms of DNA.

For the longest time, canonical DNA was considered an inert molecule with just one type of structure. Science limited itself by looking at DNA as just a series of sequences of different base pairs storing genetic information. Contrary to that, DNA is a dynamic, vibrant molecule with the potential for many different structures that regulate the expression of the genome and proteome. Conformational transitions from the canonical right-handed double-stranded (ds) B-DNA structure can convert into alternative molecules, such as left-handed ds-Z-DNA, which have important biological functions. This collection of exotic nucleic acids extends to triplex DNA, quadruplex DNA, hairpin DNA, and cruciform DNA. This most recent discovery is yet another example of how DNA can adopt diverse configurations during its involvement in molecular biological processes such as cellular replication, transcription, recombination, and repair. Until now, only G-quadruplexes were believed to have biological functions, but now sets of cytosines can adopt the quadruplex DNA structure—namely, i-motifs.

Many of these exotic DNA configurations have been associated with genetic disorders and cancers. This makes them a target for nucleic acid structure-specific drug discovery. The more science learns about noncanonical nucleic acid structures and their biological functions, the more likely we will approach a new frontier in molecular biology, which examines how proteins and small-molecule drugs interact with these exotic in vivo nucleic acids. Discoveries like this will help foster a greater understanding of nucleic acid primary, secondary, tertiary, and quaternary structures. More discoveries of new exotic DNA and RNA structures will bring us closer to eventually deciphering all aspects of the human and nonhuman genomes. More emphasis must be placed on the structural and chemical significance of exotic nucleic acid structures if we want to fully understand all aspects of molecular biology in the human cell. For this reason we should congratulate the research team for their outstanding discovery and advances toward the identification of a novel DNA structure.

Claude E. Gagna
Bronxville, N.Y.

Correction:
May 28, page 6: In the news story on the new class of isomers, the subheadline incorrectly describes the molecule’s bond-angle inversion as irreversible. The inversion is not irreversible.