Structural insights into the morpholino nucleic acid/RNA duplex using the new XNA builder Ducque in a molecular modeling pipeline.

The field of synthetic nucleic acids with novel backbone structures [xenobiotic nucleic acids (XNAs)] has flourished due to the increased importance of XNA antisense oligonucleotides and aptamers in medicine, as well as the development of XNA processing enzymes and new XNA genetic materials. Molecular modeling on XNA structures can accelerate rational design in the field of XNAs as it contributes in understanding and predicting how changes in the sugar-phosphate backbone impact on the complementation properties of the nucleic acids. To support the development of novel XNA polymers, we present a first-in-class open-source program (Ducque) to build duplexes of nucleic acid analogs with customizable chemistry.

Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif.

Nucleic acids not only form the basis of heredity, but are increasingly a source of novel nano-structures, -devices and drugs. This has spurred the development of chemically modified alternatives (xeno nucleic acids (XNAs)) comprising chemical configurations not found in nature to extend their chemical and functional scope. XNAs can be evolved into ligands (XNA aptamers) that bind their targets with high affinity and specificity.

Efficient and Accurate Potential Energy Surfaces of Puckering in Sugar-Modified Nucleosides.

Puckering of the sugar unit in nucleosides and nucleotides is an important structural aspect that directly influences the helical structure of nucleic acids. The preference for specific puckering modes in nucleic acids can be analyzed via conformational analysis, but the large amount of conformations and the accuracy of the analysis leads to an extensive amount of computational time. In this paper, we show that the combination of geometry optimizations with the HF-3c method with single point energies at the RI-MP2 level results in accurate results for the puckering potential energy surface (PES) of DNA and RNA nucleosides while significantly reducing the necessary computational time.

Stable Hairpin Structures Formed by Xylose-Based Nucleic Acids.

Xenobiology explores synthetic nucleic acid polymers as alternative carriers of genetic information to expand the central dogma. The xylo- and deoxyxylo-nucleic acids (XyNA and dXyNA), containing 3' epimers of riboses and deoxyriboses, are considered to be potential candidates for an orthogonal system. In this study, thermal and spectroscopic analyses show that XyNA and dXyNA form stable hairpins.

Phenyltriazole-functionalized sulfamate inhibitors targeting tyrosyl- or isoleucyl-tRNA synthetase.

Antimicrobial resistance is considered as one of the major threats for the near future as the lack of effective treatments for various infections would cause more deaths than cancer by 2050. The development of new antibacterial drugs is considered as one of the cornerstones to tackle this problem. Aminoacyl-tRNA synthetases (aaRSs) are regarded as good targets to establish new therapies.

An N-terminal Ca-binding motif regulates the secretory pathway Ca/Mn-transport ATPase SPCA1.

The Ca/Mn transport ATPases 1a and 2 (SPCA1a/2) are closely related to the sarco(endo)plasmic reticulum Ca-ATPase (SERCA) and are implicated in breast cancer and Hailey-Hailey skin disease. Here, we purified the human SPCA1a/2 isoforms from a yeast recombinant expression system and compared their biochemical properties after reconstitution. We observed that the purified SPCA1a displays a lower Ca affinity and slightly lower Mn affinity than SPCA2.