Proteolytic Hydrolysis of the Antitumor Peptide HLDF-6-AA in Blood Plasma
HLDF-6 hexapeptide, which corresponds to the (41)TGENHR(46) fragment of human leukemia differentiation factor (HLDF), shows a wide range of neuroprotective, normalizing, anxiolytic, nootropic and antitumor activities. A promising drug with antitumor activity is being developed based on the N-acetyl, C-amide form of HLDF-6 peptide, obtained by the solid phase method. Proteolytic hydrolysis of HLDF-6-AA peptide in blood plasma was studied using its derivatives labeled with hydrogen isotopes. The HLDF-6-AA peptide samples uniformly labeled with tritium and deuterium were obtained by the reaction of high-temperature solid-state catalytic isotope exchange at 170 degrees C. [H-3] HLDF-6-AA peptide was obtained with the molar radioactivity of 50 Ci/mmol and the average deuterium incorporation for [H-2] HLDF-6-AA peptide was 2.90 atoms per peptide molecule. Proteolytic hydrolysis of HLDF-6-AA peptide in rat blood plasma was studied using radiochromatography. It was established that the main pathway of its proteolytic hydrolysis in rat blood plasma consists in cleavage of His-Arg-NH2 (HR-NH2) dipeptide from the C-end of the amide with the half-degradation period of 35 min.