Controlling binding orientation in hairpin polyamide DNA complexes

The effects of N-terminal acetylation and C-terminal tail structure on the orientation of binding of imidazole/pyrrole polyamide DNA ligands has been investigated. We find that N-terminal acetylation leads to an intramolecular steric clash for hairpin ligands bound in the minor groove, promoting a rotation of the spatially close C-terminal pyrrole ring. This in turn leads to loss of contacts between the tail and the groove, removing the preference for 5‘-to-3‘ orientational binding typical of this class of ligand. Similarly, introduction of a glycine linker into the tail leads to a direct steric clash with the groove, again promoting rotation of the attached ligand ring. The effects of acetylation and a glycine in the tail are additive. The implications for the design of sequence-specific ligands are discussed

Controlling binding orientation in hairpin polyamide DNA complexes

The effects of N-terminal acetylation and C-terminal tail structure on the orientation of binding of imidazole/pyrrole polyamide DNA ligands has been investigated. We find that N-terminal acetylation leads to an intramolecular steric clash for hairpin ligands bound in the minor groove, promoting a rotation of the spatially close C-terminal pyrrole ring. This in turn leads to loss of contacts between the tail and the groove, removing the preference for 5‘-to-3‘ orientational binding typical of this class of ligand. Similarly, introduction of a glycine linker into the tail leads to a direct steric clash with the groove, again promoting rotation of the attached ligand ring. The effects of acetylation and a glycine in the tail are additive. The implications for the design of sequence-specific ligands are discussed

A Practical and Economical Route to (S)-Glycidyl Pivalate

An efficient method to prepare enantiopure (S)-glycidyl pivalate from (R)-epichlorohydrin and pivalic acid is reported. This work provides an alternative to the synthesis of this important building block from readily available and inexpensive materials

Structural and Substituent Group Effects on Multielectron Standard Reduction Potentials of Aromatic N‑Heterocycles

Aromatic N-heterocycles have been used in electrochemical CO₂ reduction, but their precise role is not yet fully understood. We used first-principles quantum chemistry to determine how the molecular sizes and substituent groups of these molecules affect their standard redox potentials involving various proton and electron transfers. We then use that data to generate molecular Pourbaix diagrams to find the electrochemical conditions at which the aromatic N-heterocycle molecules could participate in multiproton and electron shuttling in accordance with the Sabatier principle. While one-electron standard redox potentials for aromatic N-heterocycles can vary significantly with molecule size and the presence of substituent groups, the two-electron and two-proton standard redox potentials depend much less on structural modifications and substituent groups. This indicates that a wide variety of aromatic N-heterocycles can participate in proton, electron, and/or hydride shuttling under suitable electrochemical conditions

Species-specific population structure in rock-specialized sympatric cichlid species in Lake Tanganyika, East Africa.

Species richness and geographical phenotypic variation in East African lacustrine cichlids are often correlated with ecological specializations and limited dispersal. This study compares mitochondrial and microsatellite genetic diversity and structure among three sympatric rock-dwelling cichlids of Lake Tanganyika, Eretmodus cyanostictus, Tropheus moorii, and Ophthalmotilapia ventralis. The species represent three endemic, phylogenetically distinct tribes (Eretmodini, Tropheini, and Ectodini), and display divergent ecomorphological and behavioral specialization. Sample locations span both continuous, rocky shoreline and a potential dispersal barrier in the form of a muddy bay. High genetic diversity and population differentiation were detected in T. moorii and E. cyanostictus, whereas much lower variation and structure were found in O. ventralis. In particular, while a 7-km-wide muddy bay curtails dispersal in all three species to a similar extent, gene flow along mostly continuous habitat appeared to be controlled by distance in E. cyanostictus, further restricted by site philopatry and/or minor habitat discontinuities in T. moorii, and unrestrained in O. ventralis. In contrast to the general pattern of high gene flow along continuous shorelines in rock-dwelling cichlids of Lake Malawi, our study identifies differences in population structure among stenotopic Lake Tanganyika species. The amount of genetic differentiation among populations was not related to the degree of geographical variation of body color, especially since more phenotypic variation is observed in O. ventralis than in the genetically highly structured E. cyanostictus