Nikola Štambuk, Nevenka Kopjar, Karmela Šentija, Vera Garaj-Vrhovac, Dražen Vikić-Topić, Branka Marušić-Della Marina, Vesna Brinar, Milica Trbojević-Čepe, Neven Žarković, Božidar Ćurković, Ðurđa Babić-Naglić, Mirko Hadžija, Niko Zurak, Zdravko Brzović, Roko Martinić, Vjera Štambuk, Paško Konjevoda, Nikola Ugrinović, Ivana Pavlić-Renar, Zdenko Biđin, Biserka Pokrić, Nikola Štambuk, Nevenka Kopjar, Karmela Šentija, Vera Garaj-Vrhovac, Dražen Vikić-Topić, Branka Marušić-Della Marina, Vesna Brinar, Milica Trbojević-Čepe, Neven Žarković, Božidar Ćurković, Ðurđa Babić-Naglić, Mirko Hadžija, Niko Zurak, Zdravko Brzović, Roko Martinić, Vjera Štambuk, Paško Konjevoda, Nikola Ugrinović, Ivana Pavlić-Renar, Zdenko Biđin, and Biserka Pokrić
The structure, complementary structure and cytogenetic/proliferative effects of the Met-enkephalin on human peripheral blood lymphocytes were analyzed. Met-enkephalin, i.e. Peptid-M (LUPEX®), is a low molecular weight synthetic pentapeptide that corresponds to thymus Met-enkephalin. Its structure was examined by means of NMR spectroscopy. The influence of Met-enkephalin on in vitro normalization of chromosomally aberrant lymphocytes of patients suffering from different immune-mediated diseases, was analyzed by the sensitive cytogenetic tests for screening and detection of genome damages in human lymphocytes. The tests showed that in vitro stimulation of human lymphocytes with the Met-enkephalin led to dissapearance of different types of chromosome aberrations, reduction in the number of micronuclei, decrease in the frequency of sister chromatid exchange (SCE) and apoptosis as well as a cytostatic effect on mitosis cycles. They have also confirmed normalization of chromosomally aberrant cell findings in patients suffering from different immune-mediated diseases. These results suggest a possible role of Met-enkephalin (Peptid-M) in immunotherapy of different diseases which involve chromosomal aberrations as well as abnormal cell proliferation and offer new approaches to immunotherapy by the use of Peptid-M. Based on the molecular recognition theory and the SCA method, peptide complementary to Peptid-M was designed, synthesized and denoted Peptide-D. Peptide-D is a calpastatin fragment. Predicted ligand-receptor interaction between both peptides is confirmed by the results showing that Peptide-D blocked the Peptid-M induced lymphocyte proliferation in a dosedependent manner.