ABSTRACT
We have studied anti-tumor properties of bone marrow derived peptide Phe-Leu-Gly-Phe-Pro-Thr (MP-1) synthesized by classical methods. It was shown that MP-1 enhanced the effect ofcytostatic therapy of lymphatic leukemia P388 and increased latent growth period of P388 tumors implanted in irradiated mice. MP-1 also decreased metastasis of mouse breast adenocarcinoma Ca-755 after surgery.
Subject(s)
Antineoplastic Agents , Leukemia P388 , Oligopeptides , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cisplatin/administration & dosage , Combined Modality Therapy , Leukemia P388/drug therapy , Leukemia P388/radiotherapy , Mice , Oligopeptides/administration & dosage , Oligopeptides/chemical synthesisABSTRACT
The Val-Val-Tyr-Pro-Asp bone marrow peptide (MP-5) and an analogue (MP-5-Lys) were synthesized. Fluorescent derivatives, Ftc-MP-5 and MP-5-Lys(Ftc), were prepared. The biological activity of MP-5 and MP-5-Lys was studied in vitro and in vivo. The MP-5 peptide caused 60-84% inhibition of growth of the following mouse cancers: lymphatic leukemia P-388, melanoma B-16, and cervical carcinoma CUC-5. These peptides also restored functional activity of T lymphocytes that was inhibited by metabolic products of the HL-60 leukemic cell line. MP-5-Lys(Ftc) was shown to preserve the functional properties of MP-5 toward T lymphocytes, but Ftc-MP-5 was practically inactive.
Subject(s)
Antineoplastic Agents/chemical synthesis , Fluorescent Dyes/chemical synthesis , Immunologic Factors/chemical synthesis , Oligopeptides/chemical synthesis , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/pharmacology , Mice , Oligopeptides/chemistry , Oligopeptides/pharmacology , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Xenograft Model Antitumor AssaysABSTRACT
The bone marrow myelopeptide MP-2 (Leu-Val-Val-Tyr-Pro-Trp), exhibiting antitumor activity, and its retro-analogue (Trp-Pro-Tyr-Val-Val-Leu) were synthesized, and their properties were studied. The in vitro and in vivo activities of retro-MP-2 were comparable with those of MP-2. Both peptides equally restored the functional activity of T-lymphocytes inhibited by toxins released by HL-60 cells and inhibited by 70-82% the growth of various types of transplantable solid tumors: Ca-755 adenocarcinoma of the mammary gland, Lewis adenocarcinoma of the lung, and S180 sarcoma. The positions and intensities of the Cotton effects in CD spectra of the MP-2 peptide and its retro-analogue in various solvents are almost indistinguishable. The positions of extrema and integral intensities of the amide I and amide A bands in IR spectra of both peptides were practically identical. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 3; see also http://www.maik.ru.
Subject(s)
Adenocarcinoma/drug therapy , Adjuvants, Immunologic/chemical synthesis , Adjuvants, Immunologic/pharmacology , Carcinoma, Lewis Lung/drug therapy , Mammary Neoplasms, Experimental/drug therapy , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Adjuvants, Immunologic/chemistry , Animals , HL-60 Cells , Humans , Mice , Oligopeptides/chemistryABSTRACT
Peptide Leu-Val-Cys-Tyr-Pro-Gln, identical to the bone marrow peptide MP-3, and its Val3 and Ser3 analogs, lacking SH-group, were synthesized by conventional methods of peptide chemistry in solution and, along with the MP-3 S-S-dimerization product, were studied with respect to their effect on the macrophage phagocytic activity. It was shown that the activity was only enhanced by peptide MP-3, which demonstrated the essential role of the SH-group in this function. The dimer analog of MP-3, unlike dimer analogs of other monocysteine-containing peptides, glutathione and HP5b, did not exhibit the inhibitory effect.
Subject(s)
Macrophage Activation/drug effects , Oligopeptides/pharmacology , Sulfhydryl Compounds/pharmacology , Amino Acid Sequence , Bone Marrow/chemistry , Chromatography, High Pressure Liquid , Oligopeptides/chemical synthesis , Oligopeptides/chemistry , Sulfhydryl Compounds/chemical synthesis , Sulfhydryl Compounds/chemistrySubject(s)
Bone Marrow/chemistry , Macrophages, Peritoneal/immunology , Oligopeptides , Peptides/physiology , Phagocytosis/physiology , Animals , Dose-Response Relationship, Immunologic , Macrophages, Peritoneal/microbiology , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Peptides/chemistry , Peptides/isolation & purification , Salmonella typhimurium/immunologySubject(s)
Adjuvants, Immunologic/pharmacology , Bone Marrow/immunology , Cyclophosphamide/pharmacology , Immunosuppressive Agents/pharmacology , Oligopeptides , Peptides/pharmacology , Animals , Cell Division , Female , Immunity, Cellular/drug effects , Immunization , Lymphocyte Activation/drug effects , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Phagocytosis/drug effects , Spleen/cytology , Spleen/drug effectsABSTRACT
The cells of intact spinal cord produce a group of biologically active peptides--myelopeptides (MP) stimulating antibody formation at peak of immune response and exerting an analgesic endorphin-like effect. The experiments on comparative studies of antibody-stimulating effect of synthetic opioid peptides and MP have shown that the mixture of opioid substances composed in aliquots corresponding to their content in MP has an antibody-stimulating effect similar to that of MP. Synthetic beta-endorphin also enhances the antibody formation during the productive phase of immune response at doses 1000-fold lower than its MP level. Leu- and met-enkephalins have no antibody-stimulating effect. An antagonist opiate, naloxone, blocks the antibody-stimulating activity of both opiates and MP. A close correlation between antibody-stimulating and analgetic endorphin-like MP activity has been established.