Templating Peptide Chemistry with Nucleic Acids: Toward Artificial Ribosomes, Cell-Specific Therapeutics, and Novel Protein-Mimetic Architectures.

In biology, nanomachines like the ribosome use nucleic acid templates to synthesize polymers in a sequence-specific, programmable fashion. Researchers have long been interested in using the programmable properties of nucleic acids to enhance chemical reactions via colocalization of reagents using complementary nucleic acid handles. In this review, we describe progress in using nucleic acid templates, handles, or splints to enhance the covalent coupling of peptides to other peptides or oligonucleotides.

Site-Specific Arrangement and Structure Determination of Minor Groove Binding Molecules in Self-Assembled Three-Dimensional DNA Crystals.

The structural analysis of guest molecules in rationally designed and self-assembling DNA crystals has proven an elusive goal since its conception. Oligonucleotide frameworks provide an especially attractive route toward studying DNA-binding molecules by using three-dimensional lattices with defined sequence and structure. In this work, we site-specifically position a suite of minor groove binding molecules, and solve their structures via X-ray crystallography as a proof-of-principle toward scaffolding larger guest species.

Site-specific arrangement and structure determination of minor groove binding molecules in self-assembled three-dimensional DNA crystals.

The structural analysis of guest molecules in rationally designed and self-assembling DNA crystals has proven elusive since its conception. Oligonucleotide frameworks provide an especially attractive route towards studying DNA-binding molecules by using three-dimensional lattices with defined sequence and structure. In this work, we site-specifically position a suite of minor groove binding molecules, and solve their structures via x-ray crystallography, as a proof-of-principle towards scaffolding larger guest species.

Proximity-enhanced synthesis of DNA-peptide-DNA triblock molecules.

We report a proximity-enhanced method to synthesize a peptide flanked by two different oligonucleotide handles. Our method relies on sequential bioorthogonal reactions, and partial hybridization of the second handle to the first. We demonstrate the synthesis of a protease-responsive DNA "latch" and a cyclic bioactive peptide using this method.