Photochemical Dimerization of Plakinidine B Leads to Potent Inhibition of the E3 Ubiquitin-Protein Ligase CBL-B

Org Lett. 2022 Dec 30;24(51):9468-9472. doi: 10.1021/acs.orglett.2c03922. Epub 2022 Dec 14.

Abstract

A new dimeric alkaloid plakoramine A [(±)-1] was identified from a marine sponge Plakortis sp. Chiral-phase HPLC separation of (±)-1 led to the purified enantiomers (+)-1 and (-)-1 which both potently inhibited CBL-B E3 ubiquitin ligase activities. The absolute configurations of the enantiomers were determined by quantum chemical calculations. Scrutinization of the purification conditions revealed a previously undescribed, nonenzymatic route to form (±)-1 via photochemical conversion of its naturally occurring monomeric counterpart, plakinidine B (2).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Dimerization*