Synthesis and Properties of the retro-Analogue of Myelopeptide MP-2

Abstract

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.

Marine antimicrobial peptide arenicin adopts a monomeric twisted β‐hairpin structure and forms low conductivity pores in zwitterionic lipid bilayers

“…Nevertheless, FTIR spectroscopy can provide unique structural information and permits to estimate the number of hydrogen‐bonded CO‐groups in a peptide backbone. The efficiency of FTIR spectra analysis was shown earlier in the studies of β‐turn‐containing peptides . An important result of this part of the work is that neither dimeric structure (formed in anionic membranes, Figure C) nor the flat β‐hairpin of arenicin‐2 (observed in DMSO solution) were revealed in PC lipid membrane.…”

“…The first band at 1626–1627 cm −1 corresponds to backbone CO‐groups in the antiparallel β‐structure (with the weak shoulder at 1694 cm −1 ), while the second one at 1677 cm −1 can be attributed to free weakly solvated amide carbonyls which are not involved in the intramolecular H‐bonds. This assignment is based on the study of cyclic and linear peptides forming β‐turns. A standard decomposition of amide I contour into Lorentz lines gives the ratio of integrated intensities of the bands due to free and H‐bonded CO‐groups shown in Table .…”

Protective effects of myelopeptides in C-1300 neuroblastoma cell line

“…The MP influence on the cell differentiation has been previously found during the investigation of the bone marrow cells of mice, cells of the bone marrow and peripheral blood of patients with hemoblastosis, and cell lines of the human myelomonoblastose HL 60 leukemia and erythroblastose K 562 leukemia [5,9,10]. These MP properties are promising for their use in the complex therapy of leukemia.…”

“…These MP properties are promising for their use in the complex therapy of leukemia. The antitumor effects of MPs to the transplantable non myeloid tumors (the Ca 755 mammary adenocarcinoma, the S 180 sarcoma, the B 16 melanoma, and a number of other cancers) depend on a normalization of the func tional activity of the immune system (for the first time, T lymphocytes [5,9,10], but not on the direct MP action on the cancer cells [11]. MPs have significantly increased the number of morphologically differenti ated neurons in the culture of the C 1300 neuroblas toma (Fig.…”