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Synthesis and In Vitro Neuroprotector Activity of Diastereoisomers of a Dimeric Dipeptide Mimetic of Nerve Growth Factor GK-2.
- Source :
-
Pharmaceutical Chemistry Journal . Nov2018, Vol. 52 Issue 8, p704-710. 7p. - Publication Year :
- 2018
-
Abstract
- Previously, a dimeric dipeptide mimetic bis-(N-monosuccinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2) based on the β-turn of the fourth loop of nerve growth factor was prepared by us, activated TrkA, and exhibited neuroprotective activity in vitro (10-5 - 10-9 M) and in vivo (0.05 - 5 mg/kg i.p.). The present work reports the synthesis of two of its diastereomers, bis-(N-monosuccinyl-L-glutamyl-D-lysine) (GK-2LD) and bis-(N-monosuccinyl-D-glutamyl-L-lysine) hexamethylenediamides (GK-2DL). Studies of their neuroprotective activities using HT-22 neuronal culture under oxidative stress showed that switching L-lysine to D-lysine led to a significant activity decrease whereas switching L-glutamic acid to the D-stereoisomer caused it to disappear completely. Both dipeptide residues were concluded to be involved in interactions with the TrkA receptor. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DIASTEREOISOMERS
*NEUROLOGY
*PEPTIDES
*NERVE growth factor
*OXIDATIVE stress
Subjects
Details
- Language :
- English
- ISSN :
- 0091150X
- Volume :
- 52
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Pharmaceutical Chemistry Journal
- Publication Type :
- Academic Journal
- Accession number :
- 134038880
- Full Text :
- https://doi.org/10.1007/s11094-018-1885-3