New labeled derivatives of the neuroprotective peptide colivelin: synthesis, characterization, and first in vitro and in vivo applications.

Abstract

Colivelin (CL), first reported in 2005, is the most potent member of the humanin family of neuroprotective peptides with in vitro and in vivo rescuing action against insults associated with Alzheimer's disease (AD). The objective of the present work is the design, synthesis and characterization of specific CL derivatives that can be used as molecular probes in the investigation of the unknown mechanism of CL action. Within this framework, three CL derivatives bearing suitable tags, i.e., the fluorescent moiety FITC, the streptavidin-counterpart biotinyl-group, and the (99m)Tc-radiometal chelating unit dimethylGly-Ser-Cys, were developed and subsequently applied in biological evaluation experiments. Specifically, the FITC-labeled derivative of CL was used in confocal microscopy, where specific binding at the periphery of F11 cells was observed; the biotin-labeled derivative of CL was used in an in-house developed ELISA-type assay, where specific and concentration-dependent binding with the β-amyloid peptide of AD was shown; finally, the (99m)Tc-radiolabeled derivative of CL was used in in vivo biodistribution studies in healthy Swiss Albino mice, where 0.58% of the radioactivity administered was measured in the mouse brain 2min after injection. The above first successful applications of the CL probes demonstrate their potential to contribute in the field of neuroprotective peptides.

• Authors: Myrta Kostomoiri, Christos Zikos, Dimitra Benaki, Charalampos Triantis, Marina Sagnou, Maria Paravatou-Petsotas, Amalia Papadaki, Haralabia Boleti, Minas Papadopoulos, Ioannis Pirmettis, Maria Pelecanou, Evangelia Livaniou
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 567 Pg. 83-93 (Feb 01 2015) ISSN: 1096-0384 [Electronic] United States
• PMID: 25575783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Colivelin
• Intracellular Signaling Peptides and Proteins
• Molecular Probes
• Neuroprotective Agents
• Technetium

Topics

• Amino Acid Sequence
• Animals
• Chemistry Techniques, Synthetic
• Drug Design
• Ganglia, Spinal (cytology)
• Intracellular Signaling Peptides and Proteins (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Male
• Mice
• Microscopy, Fluorescence
• Molecular Probes (chemistry)
• Molecular Sequence Data
• Neurons (cytology, drug effects)
• Neuroprotective Agents (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Rats
• Technetium (chemistry)