Secondary Structure of DNA Aptamer Influences Biomimetic Mineralization of Calcium Carbonate.

Calcium materials, such as calcium carbonate, are produced in natural and industrial settings that range from oceanic to biomedical. An array of biological and biomimetic template molecules have been employed in controlling and understanding the mineralization reaction but have largely focused on small molecule additives or disordered polyelectrolytes. DNA aptamers are synthetic and programmable biomolecules with polyelectrolyte characteristics but with predictable and controllable secondary structure akin to native extracellular moieties. This work demonstrates for the first time the influence of DNA aptamers with known G-quadruplex structures on calcium carbonate mineralization. Aptamers demonstrate kinetic inhibition of mineral formation, sequence and pH-dependent uptake into the mineral, and morphological control of the primarily calcite material in controlled solution conditions. In reactions initiated from the complex matrix of ocean water, DNA aptamers demonstrated enhancement of mineralization kinetics and resulting amorphous material. This work provides new biomimetic tools to employ in controlled mineralization and demonstrates the influence that template secondary structure can have in material formation.

On-resin Cα-functionalization of N-arylglycinyl peptides with boronic acids.

A late-stage α-C-H functionalization reaction of resin-bound, electron-rich N-aryl peptides with boronic acid nucleophiles under mild conditions is reported. We explore the impact of the N-arylglycinyl peptide structure on reactivity, and present a scope of the optimized reaction where both the peptide sequence and nature of boronic acid derivatives are varied.

N-Arylation of Amino Acid Esters to Expand Side Chain Diversity in Ketoxime Peptide Ligations.

Palladium-catalyzed N-arylations of amino acid tert-butyl esters using 4-bromo-N,N-dimethylaniline as a coupling partner are reported. The resulting N-aryl amino acid esters are suitable building blocks for the synthesis of electron-rich N-aryl peptides, which undergo oxidative couplings to aminooxy groups to afford ketoxime peptides under mild conditions. N-aryl amino acid tert-butyl esters possessing unnatural side chains were also accessed via glycine Schiff base alkylation, further increasing the scope of Cα-substitution in ketoxime peptides.

Ketoxime peptide ligations: oxidative couplings of alkoxyamines to N-aryl peptides.

Chemoselective ligation methods that preserve or introduce side chain diversity are critical for chemical synthesis of peptides and proteins. Starting from ketone substrates instead of aldehydes in oxime ligation reactions would allow substitution at the site of ligation; however, synthetic challenges to readily access ketone derivatives from common amino acid building blocks have precluded the widespread use of ketoxime peptide ligation reactions thus far. Moreover, ketones are typically much slower to react in condensation reactions compared to aldehydes. Here, one-pot catalyst-free oxidative couplings of α-substituted N-aryl peptides with alkoxyamines provide access to oxime linkages with diverse side chains. Electron-rich N-(p-Me2N-phenyl)-amino acids possessing substituents at the α-carbon were found to be uniquely capable of undergoing site-selective α-C-H oxidations in situ under an O2 atmosphere at neutral pH. Comparative studies with N-arylglycinyl peptides revealed that substitution at the α-carbon caused notable changes in reactivity, with greater sensitivity to solvent and buffer salt composition.