[The binding of Semax, ACTH 4-10 heptapeptide, to plasma membranes of the rat forebrain basal nuclei and its biodegradation].
Dolotov. O V OV; Zolotarev. Iu A IuA; Dorokhova. E M EM; Andreeva. L A LA; Alfeeva. L Iu LIu; Grivennikov. I A IA; Miasoedov. N F NF
Key Findings
- Semax binds specifically to rat forebrain basal nuclei membranes with high affinity (Kd ≈2.4 nM).
- Binding is calcium‑dependent, reversible, and shows about 33.5 × 10⁻¹⁵ mol/mg protein sites.
- In membrane preparations Semax’s half‑life exceeds 1 hour and it is mainly degraded by dipeptidylaminopeptidases into a pentapeptide and then a tripeptide.
Practical Outcomes
- Semax appears relatively stable in brain tissue for at least an hour, suggesting any dosing schedule should consider a similar duration of action. The degradation pathway hints that inhibitors of dipeptidylaminopeptidases might extend its effects, but human data are lacking, so no concrete protocol changes can be recommended yet.
Summary
The study shows that Semax, a short peptide, sticks tightly to rat brain membrane sites with nanomolar strength, needs calcium to bind, and stays around for over an hour before being broken down by specific enzymes into smaller pieces.
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.
Study Information
pubmed
2004
10.1023/b:rubi.0000030127.46845.f0