New Peptidic Neuroprotectants Against NMDA Neurotoxicity: Syntheses and Biological Evaluations of Linear Complestatin Analogs

Ho-Joon      Park; Seung-Woo      Kim; Young-Gyun      Shin; Yun-Jung      Kim; Ja-Kyeong      Lee; Suk   Bin   Kong; Sung-Hwa      Yoon

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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Letters in Drug Design & Discovery

Title: New Peptidic Neuroprotectants Against NMDA Neurotoxicity: Syntheses and Biological Evaluations of Linear Complestatin Analogs

Volume: 5 Issue: 2

Author(s): Ho-Joon Park, Seung-Woo Kim, Young-Gyun Shin, Yun-Jung Kim, Ja-Kyeong Lee, Suk Bin Kong and Sung-Hwa Yoon

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Keywords: NMDA, Neurotoxicity, Complestatin, LDH release, 3,5-dichloro-4-hydroxyphenylglycine

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.

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Park Ho-Joon, Kim Seung-Woo, Shin Young-Gyun, Kim Yun-Jung, Lee Ja-Kyeong, Kong Bin Suk and Yoon Sung-Hwa, New Peptidic Neuroprotectants Against NMDA Neurotoxicity: Syntheses and Biological Evaluations of Linear Complestatin Analogs, Letters in Drug Design & Discovery 2008; 5 (2) . https://dx.doi.org/10.2174/157018008783928526