ABSTRACT
Granulocytic CSF pegylated using electron-beam synthesis nanotechnology exhibits pronounced granulomonocytopoiesis-stimulating and SC-mobilizing activity. More potent stimulation of committed precursors against the background of less pronounced activation of polypotent hemopoietic cells is a peculiarity of hemostimulating action of pegylated using electron-beam synthesis nanotechnology granulocytic CSF in comparison with its non-modified analog. The mobilizing effect of pegylated using electron-beam synthesis nanotechnology granulocytic CSF on early progenitor elements surpasses that of non-conjugated cytokine.
Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacology , Hematinics/pharmacology , Polyethylene Glycols/pharmacology , Animals , Bone Marrow/drug effects , Bone Marrow Cells/drug effects , Cell Count , Cyclophosphamide/pharmacology , Granulocyte Colony-Stimulating Factor/chemical synthesis , Granulocytes/cytology , Granulocytes/drug effects , Hematinics/chemical synthesis , Hematopoiesis/drug effects , Humans , Immunosuppressive Agents/pharmacology , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/physiology , Mice , Mice, Inbred CBA , Nanotechnology , Neutrophils/cytology , Neutrophils/drug effects , Poisson Distribution , Polyethylene Glycols/chemical synthesis , Statistics, NonparametricSubject(s)
Iron-Dextran Complex/adverse effects , Animals , Carcinogenicity Tests , Carcinogens/chemical synthesis , Carcinogens/chemistry , Carcinogens/pharmacology , Carcinogens/toxicity , Cricetinae , Female , Government Regulation , Guidelines as Topic , Hematinics/adverse effects , Hematinics/chemical synthesis , Hematinics/chemistry , Hematinics/toxicity , Humans , Iron-Dextran Complex/chemical synthesis , Iron-Dextran Complex/chemistry , Iron-Dextran Complex/toxicity , Male , Mice , Occupational Exposure/adverse effects , Occupational Exposure/legislation & jurisprudence , Rabbits , Rats , United StatesABSTRACT
A series of TAN-1511 analogues bearing a non-peptide spacer in place of the Gly-Gly-Gly sequence in the peptide moiety was synthesized, and the effects of these compounds on the proliferation of bone marrow cells in culture and experimental leukocytopenia in mice were examined. The structure-activity relationships obtained were as follows. As the substituent at the 2-position of the 4-thiaheptanoic acid framework, an amino group, methyl group or hydrogen was preferable; as a spacer in place of the Gly-Gly-Gly sequence, a 4-aminobenzoyl or 4-aminomethylbenzoyl group was suitable; and as the fatty acids bonded to the 6,7-dihydroxy groups, C16 fatty acid was best. Compounds 12f, 30d and 30i potently promoted the proliferation of bone marrow cells in culture and the restoration of leukocyte counts in a murine leukocytopenia model.
