| dc.contributor.author | Kilgore, Henry R | |
| dc.contributor.author | Olsson, Chase R | |
| dc.contributor.author | D’Angelo, Kyan A | |
| dc.contributor.author | Movassaghi, Mohammad | |
| dc.contributor.author | Raines, Ronald T | |
| dc.date.accessioned | 2021-12-07T15:27:42Z | |
| dc.date.available | 2021-10-27T20:31:14Z | |
| dc.date.available | 2021-12-07T15:27:42Z | |
| dc.date.issued | 2020-09 | |
| dc.identifier.issn | 0002-7863 | |
| dc.identifier.uri | https://hdl.handle.net/1721.1/136169.2 | |
| dc.description.abstract | Copyright © 2020 American Chemical Society. Epithiodiketopiperazines (ETPs) are a structurally complex class of fungal natural products with potent anticancer activity. In ETPs, the diketopiperazine ring is spanned by a disulfide bond that is constrained in a high-energy eclipsed conformation. We employed computational, synthetic, and spectroscopic methods to investigate the physicochemical attributes of this atypical disulfide bond. We find that the disulfide bond is stabilized by two n→π∗ interactions, each with large energies (3-5 kcal/mol). The n→π∗ interactions in ETPs make disulfide reduction much more difficult, endowing stability in physiological environments in a manner that could impact their biological activity. These data reveal a previously unappreciated means to stabilize a disulfide bond and highlight the utility of the n→π∗ interaction in molecular design. | en_US |
| dc.language.iso | en | |
| dc.publisher | American Chemical Society (ACS) | en_US |
| dc.relation.isversionof | 10.1021/JACS.0C06477 | en_US |
| dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
| dc.source | PMC | en_US |
| dc.title | n →π* Interactions Modulate the Disulfide Reduction Potential of Epidithiodiketopiperazines | en_US |
| dc.type | Article | en_US |
| dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | |
| dc.relation.journal | Journal of the American Chemical Society | en_US |
| dc.eprint.version | Author's final manuscript | en_US |
| dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
| eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
| dc.date.updated | 2021-09-09T15:10:04Z | |
| dspace.orderedauthors | Kilgore, HR; Olsson, CR; D’Angelo, KA; Movassaghi, M; Raines, RT | en_US |
| dspace.date.submission | 2021-09-09T15:10:06Z | |
| mit.journal.volume | 142 | en_US |
| mit.journal.issue | 35 | en_US |
| mit.license | OPEN_ACCESS_POLICY | |
| mit.metadata.status | Authority Work Needed | en_US |
