The effects of the EW dipeptide optical and chemical isomers on the CFU-S population in intact and irradiated mice.
The influence of Glu-Trp (EW) synthetic dipeptide isomers on hemopoietic progenitor cells and certain immune response reactions is determined by their optical and chemical properties. Thus, the all L-amino acid containing dipeptides L-Glu-L-Trp and L-gammaGlu-L-Trp have no effect on proliferation of committed and pluripotent CFU-S in intact bone marrow. The optical isomers of the Glu residue are an essential determinant of the EW dipeptide biological activity. The inversion of the amino acid optical form imparts suppressor properties: D-Glu-D-Trp,D--gammaGlu-D-Trp, D-Glu-L-Trp and D-gammaGlu-L-Trp inhibit proliferation of hemopoietic progenitors in intact bone marrow. The type of the peptide bond between L-Glu and Trp is another important factor for the biological activity of the L-Glu-containing peptides. Unlike L-Glu-D-Trp with alpha-peptide bond, the dipeptide L-gammaGlu-D-Trp with gamma-peptide bond stimulates CFU-S-8 proliferation in intact bone marrow. The diverse effects of the EW optical isomers on hemopoietic progenitors underlie the radioprotective properties of the D-Glu-containing dipeptides and the radiotherapeutic ones of the L-Glu dipeptides. In animals, pre-irradiation injection of D-Glu-D-Trp, D-gammaGlu-D-Trp, D-Glu-L-Trp, D-gammaGlu-L-Trp, or post-irradiation injection of L-Glu-L-Trp, L-gammaGlu-L-Trp promoted regeneration of the hemopoietic progenitor population.
Deigin
V I
VI
Department of Peptide Chemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia. immunotech@ica.net <immunotech@ica.net>
Semenets
T N
TN
Zamulaeva
I A
IA
Maliutina
Ya V
YV
Selivanova
E I
EI
Saenko
A S
AS
Semina
O V
OV
D000818:Animals; D001854:Bone Marrow Cells / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013237:Stereoisomerism
D004151:Dipeptides; C057081:alpha-glutamyltryptophan