A research team at the University of Cologne has developed an artificial DNA base pair that works according to a new chemical principle. In contrast to natural bases, the novel artificial base pairs u...

The past decades have seen significant expansion of the nucleic acid space with the development of modified artificial base pairs based on natural nucleic acid analogues and even entirely new designed base pairs. This expansion has led to tremendous potential for applications such as site-specific labeling and structural investigations. However, natural nucleic acids rely strongly on hydrogen bonding as the attraction force, which has driven the development of artificial base pairs that adapt this mechanism. To achieve orthogonality with natural bases, unnatural base pairs with alternative attraction forces, such as hydrophobic interactions, have been developed which however can perturb duplex structures. Our work introduces a completely newly designed artificial base pair that leverages halogen bonding (R–Hal···) as a directional hydrogen bonding-like interaction. We report computational studies that led to the development of this novel unnatural base pair and its synthesis. Our results demonstrate the successful acceptance of a bulky iodinated nucleoside triphosphate by KlenTaq DNA polymerase, enabling the selective enzymatic synthesis of a DNA strand containing the dIIPO–doIPP base pair. Our work presents the first demonstration of a novel base pair with halogen bonding potential that is enzymatically incorporated into DNA.

Artificial base-pairs expand the genetic alphabet and allow for site-specific labeling, for example with fluorophores or spin labels, thereby enhancing the capabilities of biomolecular sensing. We…

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Nucleic acid sensing is crucial for advancing diagnostics, therapeutic monitoring, and molecular biology research by enabling the precise identification of DNA and RNA interactions. Here, we present an innovative sensing platform based on DNA-functionalized whispering gallery mode (WGM) microlasers. By correlating spectral shifts in laser emission to changes in the refractive index, we demonstrate real-time detection of DNA hybridization and structural changes. The addition of gold nanoparticles to the DNA strands significantly enhances sensitivity, and exclusively labeling the sensing strand or a hairpin strand eliminates the need for secondary labeling of the target strand. We further show that ionic strength influences DNA compactness, and we introduce a hairpin-based system as a dual-purpose sensor and controlled release mechanism for drug delivery. This versatile WGM-based platform offers promise for sequence-specific nucleic acid sensing, multiplexed detection, and in vivo applications in diagnostics and cellular research.