CYTOGENETIC EFFECTS OF MET-ENKEPHALIN (PEPTID-M) ON HUMAN-LYMPHOCYTES

The structure, complementary structure and cytogenetic/proliferative e ffects of the Met-enkephalin on human peripheral blood lymphocytes wer e analyzed. Met-enkephalin, i.e. Peptid-M (LUPEX(R)), is a low molecul ar weight synthetic pentapeptide that corresponds to thymus Met-enkeph alin, Its structure was examined by means of NMR spectroscopy. The inf luence of Met-enkephalin on in vitro normalization of chromosomally ab errant lymphocytes of patients suffering from different immune-mediate d diseases, was analyzed by the sensitive cytogenetic tests for screen ing and detection of genome damages in human lymphocytes. The tests sh owed that in vitro stimulation of human lymphocytes with the Met-enkep halin led to disappearance of different types of chromosome aberration s, reduction in the number of micronuclei, decrease in the frequency o f sister chromatid exchange (SCE) and apoptosis as well as a cytostati c effect on mitosis cycles. They have also confirmed normalization of chromosomally aberrant cell findings in patients suffering from differ ent immune-mediated diseases. These results suggest a possible role of Met-enkephalin (Peptid-M) in immunotherapy of different diseases whic h involve chromosomal aberrations as well as abnormal cell proliferati on and offer new approaches to immunotherapy by the use of Peptid-M. B ased on the molecular recognition theory and the SCA method, peptide c omplementary to Peptid-M was designed, synthesized and denoted Peptide -D. Peptide-D isa calpastatin fragment. Predicted ligand-receptor inte raction between both peptides is confirmed by the results showing that Peptide-D blocked the Peptid-M induced lymphocyte proliferation in a dose-dependent manner.