The PA207 peptide inhibitor of LIM-only protein 2 (Lmo2) targets zinc finger domains in a non-specific manner

Peptide aptamers of lim-only protein 2 (lmo2) were previously used to successfully treat lmo2-induced tumours in a mouse model of leukaemia. here we show that the lmo2 aptamer pa207,either as a free peptide or fused to thioredoxin trx-pa207,causes purified lmo2 to precipitate rather than binding to a defined surface on the protein. stabilisation of lmo2 through interaction with lim domain binding protein 1 (ldb1),a normal binding partner of lmo2,abrogates this effect. the addition of free zinc causes trx-pa207 to self associate,suggesting that pa207 destabilises lmo2 by modulating normal zinc-coordination in the lim domains. gst-pulldown experiments with other lmo and gata proteins indicates that pa207 can bind to a range of zinc finger proteins. thus,pa207 and other cysteine-containing peptide aptamers for lmo2 may form a class of general zinc finger inhibitors. © 2014 bentham science publishers.