PE-22-28

PE-22-28 is a seven-amino-acid peptide designed from spadin, a 17-residue peptide also called PE 12-28. Spadin is released from the propeptide produced when neurotensin receptor 3 (NTSR3, also known as sortilin) matures. Investigators designed PE 22-28 after identifying the products formed when spadin breaks down in blood, with the aim of extending spadin's short in vivo duration of action. Its molecular target is TREK-1, a two-pore-domain (K2P) potassium channel.

PE-22-28 in the research literature

In patch-clamp recordings from HEK cells expressing TREK-1, PE 22-28 inhibited the channel with an IC50 of 0.12 nM, while spadin gave 40-60 nM in the same system. Various modifications to the N- or C-terminus either kept or abolished channel inhibition without changing binding affinity. In mice, the reported duration of action extended to about 23 hours, against 7 hours for spadin. PE 22-28 and its analogs increased PSD-95 expression in cultured mouse cortical neurons and were associated with hippocampal neurogenesis after four days.

In studies of the parent peptide, spadin bound TREK-1 with an affinity of about 10 nM and blocked TREK-1 currents in COS-7 cells and hippocampal neurons. It did not inhibit the related K2P channels TREK-2, TRAAK, TASK or TRESK.