A novel retro-inverso peptide is a preferential JNK substrate-competitive inhibitor

- A d-amino acid peptide D-PYC98 is a 5-fold more potent JNK inhibitor than L-PYC98.
- D-PYC98 is a pan JNK inhibitor that shows substrate preference.
- The related stress-activated p38α MAPK, but not ERK2 MAPK, is inhibited by D-PYC98.
- Biophysical interaction studies show direct D-PYC98-JNK1 interaction.
- TAT-conjugated D-PYC98 inhibits JNK activity in cells.