title: 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.affiliation: Institute of Biosciences & Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Myrta
authors.initials: M
authors.lastname: Kostomoiri
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Zikos
authors.affiliation: Institute of Biosciences & Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece; Department of Pharmacy, University of Athens, Panepistimioupolis, GR-15771 Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Benaki
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Triantis
authors.affiliation: Institute of Biosciences & Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Sagnou
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Paravatou-Petsotas
authors.affiliation: Intracellular Parasitism Group, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, 11521 Athens, Greece.
authors.forename: Amalia
authors.initials: A
authors.lastname: Papadaki
authors.affiliation: Intracellular Parasitism Group, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, 11521 Athens, Greece; Light Microscopy Unit, Hellenic Pasteur Institute, 127 Vas. Sofias Avenue, 11521 Athens, Greece.
authors.forename: Haralabia
authors.initials: H
authors.lastname: Boleti
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Minas
authors.initials: M
authors.lastname: Papadopoulos
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Pirmettis
authors.affiliation: Institute of Biosciences & Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece. Electronic address: pelmar@bio.demokritos.gr.
authors.forename: Maria
authors.initials: M
authors.lastname: Pelecanou
authors.affiliation: Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Livaniou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005727:Ganglia, Spinal / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D015335:Molecular Probes / Q000737:chemistry*; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013667:Technetium / Q000737:chemistry
chemical_list: C508523:Colivelin; D047908:Intracellular Signaling Peptides and Proteins; D015335:Molecular Probes; D018696:Neuroprotective Agents; D013667:Technetium
keywords: (99m)Tc-radiolabeling; Biotin labeling; Colivelin; FITC labeling; NMR; Synthetic colivelin probes