PXD051400

PXD051400 is an original dataset announced via ProteomeXchange.

Title	Catalytic Asymmetric Synthesis of meta Benzene Isosteres
Description	Aromatic rings are common elements in pharmaceutically active compounds; however, their ready oxidation can present a liability with respect to a drug's metabolic stability. Replacing these aromatic rings in pharmaceutical compounds with non-aromatic isosteric motifs can enhance properties such as potency, metabolic stability, solubility, and lipophilicity. Since the binding pockets of most pharmaceutical targets are chiral, the stereochemical configuration of the isosteric replacements are expected to have an impact on the affinity of derived ligands for target receptors. A significant impediment to this approach is the lack of simple, and scalable catalytic enantioselective syntheses of candidate isosteres from readily available precursors. In this work, we present a heretofore unknown palladium-catalyzed reaction that converts hydrocarbon-derived precursors to chiral boron-containing nortricyclanes and we show that that shape of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings. With chiral catalysts, the Pd-catalyzed reaction can be accomplished in an enantioselective fashion and subsequent transformation of the boron group provides access to a broad array of structures. We also show that incorporation of nortricyclanes into pharmaceutical motifs can result in improved biophysical properties along with stereochemistry-dependent activity. We anticipate that these features, coupled with the simple, inexpensive synthesis of the functionalized nortricyclane scaffold will render this platform a useful foundation for assembly of new biologically active agents.
HostingRepository	PRIDE
AnnounceDate	2024-09-11
AnnouncementXML	Submission_2024-09-11_02:33:33.133.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bingcong Xiong
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; biotinylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-12 08:24:11	ID requested
⏵ 1	2024-09-11 02:33:33	announced

Zhang M, Chapman M, Sarode BR, Xiong B, Liang H, Chen JK, Weerapana E, Morken JP, Catalytic asymmetric synthesis of meta benzene isosteres. Nature, 633(8028):90-95(2024) [pubmed]

10.1038/s41586-024-07865-4;

submitter keyword: ABPP, Bioisosteres,Serine Hydrolase

Eranthie Weerapana
contact affiliation	Boston College
contact email	eranthie@bc.edu
lab head
Bingcong Xiong
contact affiliation	Boston College
contact email	xiongbi@bc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/09/PXD051400

PRIDE project URI

• PRIDE
  1. PXD051400
     1. Label: PRIDE project
     2. Name: Catalytic Asymmetric Synthesis of meta Benzene Isosteres