Analogues of the neuroprotective tripeptide Gly-Pro-Glu (GPE): synthesis and structure-activity relationships

Sergio A Alonso De Diego; Pilar Muñoz; Rosario González-Muñiz; Rosario Herranz; Mercedes Martín-Martínez; Edurne Cenarruzabeitia; Diana Frechilla; Joaquín Del Río; M Luisa Jimeno; M Teresa García-López

doi:10.1016/j.bmcl.2005.03.015

Analogues of the neuroprotective tripeptide Gly-Pro-Glu (GPE): synthesis and structure-activity relationships

Bioorg Med Chem Lett. 2005 May 2;15(9):2279-83. doi: 10.1016/j.bmcl.2005.03.015.

Authors

Sergio A Alonso De Diego¹, Pilar Muñoz, Rosario González-Muñiz, Rosario Herranz, Mercedes Martín-Martínez, Edurne Cenarruzabeitia, Diana Frechilla, Joaquín Del Río, M Luisa Jimeno, M Teresa García-López

Affiliation

¹ Instituto de Química Médica, Juan de la Cierva, 3, 28006 Madrid, Spain.

PMID: 15837309
DOI: 10.1016/j.bmcl.2005.03.015

Abstract

A series of GPE analogues, including modifications at the Pro and/or Glu residues, was prepared and evaluated for their NMDA binding and neuroprotective effects. Main results suggest that the pyrrolidine ring puckering of the Pro residue plays a key role in the biological responses, while the preference for cis or trans rotamers around the Gly-Pro peptide bond is not important.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Glutamic Acid / metabolism
Indicators and Reagents
Neuroprotective Agents / chemical synthesis*
Neuroprotective Agents / chemistry
Neuroprotective Agents / pharmacology
Oligopeptides / chemical synthesis*
Oligopeptides / chemistry
Oligopeptides / pharmacology
Rats
Structure-Activity Relationship
Synaptic Membranes / drug effects
Synaptic Membranes / metabolism

Substances

Indicators and Reagents
Neuroprotective Agents
Oligopeptides
Glutamic Acid
glycyl-prolyl-glutamic acid