The Binding of Semax, ACTH 4–10 Heptapeptide, to Plasma Membranes of the Rat Forebrain Basal Nuclei and Its Biodegradation

Abstract

The binding characteristics of the peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) to plasma membranes of basal nuclei of the rat forebrain and the dynamics of its degradation during its incubation with these membranes were studied. Binding of the homogeneously labeled [G-3H]Semax was shown to be time-dependent, specific, and reversible. Specific binding of the heptapeptide depended on calcium ions and was characterized by the dissociation constant of the ligand-receptor complex Kd = 2.41 +/- 1.02 x 10(-9) M and by the concentration of binding sites Bmax = 33.5 +/- 7.9 x 10(-15) mol/mg of protein. A method of studying Semax biodegradation in the presence of plasma membranes of rat brain was developed. It is based on the use of the peptide homogeneously labeled with tritium and on an HPLC analysis with UV detection at 220 and 254 nm of the peptide fragments formed. The half-life of Semax in the presence of the plasma membranes was demonstrated to be longer than 1 h. Dipeptidylaminopeptidases are considered to be the main enzymes responsible for its biodegradation; they successively cleave Semax to the HFPGP pentapeptide and the PGP tripeptide. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia

“…Subsequently, it was demonstrated in vivo that Semax application increases both protein and mRNA levels of Bdnf, and TrkB, and mRNA level of Ngf in rat hippocampus (Dolotov et al 2006;Agapova et al 2007). At the same time, the studies of Semax degradation in rat serum and its entry to the rat brain (Potaman et al 1991(Potaman et al , 1993Dolotov et al 2004) and the studies of self-maintained effects of PGP and other proline-containing peptides (Lyapina et al 2000;Samonina et al 2001;Zhuikova et al 2003;Storozhevykh et al 2007) raise the question of whether C-terminal PGP tripeptide contributes to the effects of Semax. Recently we reported that both Semax and PGP affected the mRNA expression of some growth factors and their receptor genes under conditions of an experimental focal cerebral ischemia in rats (Dmitrieva et al 2008b).…”

ACTH6-9-PGP improves memory consolidation processes in rats

“…At the same time currently there are no data on the participation of the known MCRs in the implementation of the nootropic effect (Hoogduijn et al 2002, Hruby et al 2011. Therefore, to date, the question of the action of ACTH analogs through MCRs is still open, and it is assumed that there is at least one more undescribed subtype of receptors, through binding to which their nootropic effects can be realized (Dolotov et al 2004).…”

Pharmacotranscriptomics of peptide drugs with neuroprotective properties

“…The same authors performed a genome‐wide analysis of changes in rat brain transcriptome under the influence of PGP in pMCAO conditions 79 . Because the PGP peptide is one of the predominant derivatives of Semax in the blood plasma and brain tissue of animals, 80 it could be expected that the observed effects of Semax and PGP would be similar. However, as mentioned above, the influence of PGP on the expression levels of genes encoding growth factors only partially coincided with that of Semax 76 .…”