Abstract
Linear peptide analogs of complestatin were synthesized via solid phase peptide synthesis and tested in vitro as inhibitors against N-methyl-D-aspartic acid (NMDA) neurotoxicity as possible new peptidic neuroprotectants. While none of the analogs were as potent as the parent compound (IC50 = 2.5 μM), hexamer 11c and heptamer 1c, which contain all D-amino acids, showed modestly potent neuroprotective effects with IC50 values of 23.8 μM and 22.5 μM, respectively. The results indicate that the bicyclic ring structure of complestatin plays an important role for its inhibitory activity, and the D-stereochemistry of tryptophan (component F) is important for the potency of the linear peptide analogs. Keywords: NMDA, Neurotoxicity, Complestatin, LDH release, 3,5-dichloro-4-hydroxyphenylglycine
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