Indig F E, Pecht M, Trainin N, Burstein Y, Blumberg S
Sackler Institute of Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Biochem J. 1991 Sep 15;278 ( Pt 3)(Pt 3):891-4. doi: 10.1042/bj2780891.
A search for the natural substrates for neutral endopeptidase (NEP; EC 3.4.24.11) in the immune system led to investigation of the enzyme's action on thymic humoral factor gamma 2 (THF). The ectoenzyme rapidly and efficiently hydrolyses the Lys6-Phe7 bond of the octapeptide. The site of cleavage was confirmed by h.p.l.c. analysis, amino acid analysis and sequence determination of the products. Phosphoramidon (3.6 microM), a potent inhibitor of the enzyme, prevents this cleavage even during prolonged incubation. The high efficiency of hydrolysis of THF by NEP is similar to that reported for [Leu5]enkephalin, and the dipeptide Phe-Leu is the C-terminal product in the hydrolysis of both peptides. The presence of NEP, reportedly identified as the common acute lymphoblastic leukaemia antigen (CALLA), in bone-marrow cells and other cells of the immune system raises the possibility that it may play a role in modulating the activity of peptides such as THF.
在免疫系统中寻找中性内肽酶（NEP；EC 3.4.24.11）的天然底物，促使人们研究该酶对胸腺体液因子γ2（THF）的作用。这种外切酶能快速且高效地水解八肽的Lys6 - Phe7键。通过高效液相色谱分析、氨基酸分析及产物序列测定，证实了裂解位点。该酶的强效抑制剂磷酰胺素（3.6微摩尔）即使在长时间孵育过程中也能阻止这种裂解。NEP对THF的高效水解与报道的[亮氨酸5]脑啡肽类似，且二肽Phe - Leu是这两种肽水解的C端产物。据报道，在骨髓细胞和免疫系统的其他细胞中鉴定为常见急性淋巴细胞白血病抗原（CALLA）的NEP的存在，增加了其可能在调节诸如THF等肽的活性中发挥作用的可能性。
