Small peptides patterned after the N-terminus domain of SNAP25 inhibit SNARE complex assembly and regulated exocytosis.

摘要: Synthetic peptides patterned after the C-terminus of synaptosomal associated protein 25 kDa (SNAP25) efficiently abrogate regulated exocytosis. In contrast, use SNAP25 N-terminal-derived to modulate SNAP receptors (SNARE) complex assembly and neurosecretion has not been explored. Here, we show that N-terminus SNAP25, specially segment encompasses 22Ala-44Ile, is essential for formation SNARE complex. Peptides this domain are potent inhibitors formation. The inhibitory activity correlated with their propensity adopt an alpha-helical secondary structure. These abrogated only when added previous onset aggregate assembly. Analysis mechanism action revealed these disrupted binary formed by syntaxin. identified inhibited Ca2+-dependent exocytosis from detergent-permeabilized excitable cells. Noteworthy, amino acid sequences markedly protected intact hippocampal neurones against hypoglycaemia-induced, glutamate-mediated excitotoxicity a potency rivalled displayed botulinum neurotoxins. Our findings indicate neuronal Because in neurones, cell permeable may be hits antispasmodic analgesic drug development.