RESUMEN
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.
Asunto(s)
Antineoplásicos , Leucemia P388 , Oligopéptidos , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Línea Celular Tumoral , Cisplatino/administración & dosificación , Terapia Combinada , Leucemia P388/tratamiento farmacológico , Leucemia P388/radioterapia , Ratones , Oligopéptidos/administración & dosificación , Oligopéptidos/síntesis químicaRESUMEN
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.
Asunto(s)
Antineoplásicos/síntesis química , Colorantes Fluorescentes/síntesis química , Factores Inmunológicos/síntesis química , Oligopéptidos/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Ratones , Oligopéptidos/química , Oligopéptidos/farmacología , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adyuvantes Inmunológicos/síntesis química , Adyuvantes Inmunológicos/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Oligopéptidos/síntesis química , Oligopéptidos/farmacología , Adyuvantes Inmunológicos/química , Animales , Células HL-60 , Humanos , Ratones , Oligopéptidos/químicaRESUMEN
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.
Asunto(s)
Activación de Macrófagos/efectos de los fármacos , Oligopéptidos/farmacología , Compuestos de Sulfhidrilo/farmacología , Secuencia de Aminoácidos , Médula Ósea/química , Cromatografía Líquida de Alta Presión , Oligopéptidos/síntesis química , Oligopéptidos/química , Compuestos de Sulfhidrilo/síntesis química , Compuestos de Sulfhidrilo/químicaAsunto(s)
Médula Ósea/química , Macrófagos Peritoneales/inmunología , Oligopéptidos , Péptidos/fisiología , Fagocitosis/fisiología , Animales , Relación Dosis-Respuesta Inmunológica , Macrófagos Peritoneales/microbiología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Péptidos/química , Péptidos/aislamiento & purificación , Salmonella typhimurium/inmunologíaAsunto(s)
Adyuvantes Inmunológicos/farmacología , Médula Ósea/inmunología , Ciclofosfamida/farmacología , Inmunosupresores/farmacología , Oligopéptidos , Péptidos/farmacología , Animales , División Celular , Femenino , Inmunidad Celular/efectos de los fármacos , Inmunización , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Fagocitosis/efectos de los fármacos , Bazo/citología , Bazo/efectos de los fármacosRESUMEN
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.