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

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).

Automated summary

A new dimeric alkaloid, Plakoramine A, was discovered from a marine sponge. It showed potent inhibition of ubiquitin ligase activities. The study also revealed a previously undescribed route to form this compound through photochemical conversion.