Event Title

NMR Structural Studies of DNA Duplexes Containing Unnatural Base Pairs: dNaM-d5SICS,dNaM-dTPT3, and dCNMO-dTPT3

Loading...

Media is loading
 

Description

Unnatural base pairs formed between synthetic nucleotide analogs with hydrophobic nucleobases have been synthesized and optimized for replication, transcription, and translation in a semi-synthetic organism (SSO) by Floyd Romesberg and colleagues (Scripps Research and Synthorx). In order to provide structural insights into the unique properties of these modified duplexes, 1H NMR spectroscopic analyses with complete 2D NOESY assignments and quantitation are used to determine the spatial orientations of the unnatural bases within dodecamer duplexes. Restrained molecular dynamics simulations using Amber16 have yielded an average structure for the dNaM-d5SICS containing duplex which will be presented here. The dNaM-d5SICS containing duplex shows quite typical B-DNA structure for the Watson-Crick portions with localized perturbations in the region of the unnatural base pair extending only to the adjacent pairs. The d5SICS and dNaM moieties self-intercalate and stack with each other, as well as the nearest neighbor. We also report preliminary results on the structure determination of the dNaM-dTPT3 and dCNMO-dTPT3 containing duplexes. Given that the dCNMO-dTPT3 pair has shown the most promising ability in an SSO to store and retrieve information (in terms of the production of proteins with noncanonical amino acids, relative to dNaM-d5SICS and dNaM-dTPT3), structural comparisons may shed light on important recognition elements for the replication of unnatural base pairs.

This document is currently not available here.

Share

COinS
 

NMR Structural Studies of DNA Duplexes Containing Unnatural Base Pairs: dNaM-d5SICS,dNaM-dTPT3, and dCNMO-dTPT3

Unnatural base pairs formed between synthetic nucleotide analogs with hydrophobic nucleobases have been synthesized and optimized for replication, transcription, and translation in a semi-synthetic organism (SSO) by Floyd Romesberg and colleagues (Scripps Research and Synthorx). In order to provide structural insights into the unique properties of these modified duplexes, 1H NMR spectroscopic analyses with complete 2D NOESY assignments and quantitation are used to determine the spatial orientations of the unnatural bases within dodecamer duplexes. Restrained molecular dynamics simulations using Amber16 have yielded an average structure for the dNaM-d5SICS containing duplex which will be presented here. The dNaM-d5SICS containing duplex shows quite typical B-DNA structure for the Watson-Crick portions with localized perturbations in the region of the unnatural base pair extending only to the adjacent pairs. The d5SICS and dNaM moieties self-intercalate and stack with each other, as well as the nearest neighbor. We also report preliminary results on the structure determination of the dNaM-dTPT3 and dCNMO-dTPT3 containing duplexes. Given that the dCNMO-dTPT3 pair has shown the most promising ability in an SSO to store and retrieve information (in terms of the production of proteins with noncanonical amino acids, relative to dNaM-d5SICS and dNaM-dTPT3), structural comparisons may shed light on important recognition elements for the replication of unnatural base pairs.