Tubulin is the target binding site for NAP-related peptides: ADNF-9, D-NAP, and D-SAL.

The authors set out to investigate whether NAP-related peptides interact with tubulin at a NAP binding site. Previous studies have shown that the neuroprotective peptide NAP binds to tubulin. As NAP (NAPVSIPQ) shares structural similarities with ADNF-9 (SALLRSIPA), and the all-D-enantiomers, D-NAP and D-SAL, it was hypothesized that all of these peptides compete with NAP-tubulin binding. Using NAP affinity column and extracts from newborn rat brain (cerebral cortex), we now show that the above-mentioned peptides compete with NAP binding to tubulin. The identification of tubulin as a target binding site for NAP-related peptides explains, in part, the broad neuroprotective activity offered by these potent peptides.