Blishchenko Elena Y, Sazonova Olga V, Kalinina Olga A, Yatskin Oleg N, Philippova Marina M, Surovoy Andrei Y, Karelin Andrei A, Ivanov Vadim T
Group of Protein Research, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow, Russia.
Peptides. 2002 May;23(5):903-10. doi: 10.1016/s0196-9781(02)00017-7.
Hemorphins, i.e. endogenous fragments of beta-globin chain segment (32-41) LVVYPWTQRY(F) suppress the growth of transformed murine fibroblasts L929 cell culture, the effect is due to cytotoxicity and inhibition of cell proliferation. The contribution of cytotoxicity depends on the presence of Leu(32): VV-hemorphins, except VV-hemorphin-4, exhibit cytotoxicity significantly higher than respective LVV-hemorphins. Decrease of cell number induced by hemorphins depend on the extent of N- and C-terminal degradation of hemorphins: VV-hemorphins in most cases are more active than LVV-, V-hemorphins, and hemorphins. In the group of VV-hemorphins the activity of VV-hemorphin-5 (valorphin) is significantly higher than of VV-hemorphin-7, VV-hemorphin-6, and VV-hemorphin-4, meaning that the presence of C-terminal Gln is important for suppressing of cell number. The amino acid sequence VVYPWTQ corresponding to valorphin was identified as important for manifestation of the both cytotoxic and antiproliferative effects.
血啡肽,即β-珠蛋白链片段(32 - 41)LVVYPWTQRY(F)的内源性片段,可抑制转化的小鼠成纤维细胞L929细胞培养物的生长,其作用归因于细胞毒性和对细胞增殖的抑制。细胞毒性的作用取决于亮氨酸(32)的存在:除了血啡肽-4外,VV - 血啡肽的细胞毒性显著高于相应的LVV - 血啡肽。血啡肽诱导的细胞数量减少取决于血啡肽N端和C端降解的程度:在大多数情况下,VV - 血啡肽比LVV - 、V - 血啡肽及血啡肽更具活性。在VV - 血啡肽组中,VV - 血啡肽-5(缬啡肽)的活性显著高于VV - 血啡肽-7、VV - 血啡肽-6和VV - 血啡肽-4,这意味着C端谷氨酰胺的存在对抑制细胞数量很重要。与缬啡肽对应的氨基酸序列VVYPWTQ被确定为对细胞毒性和抗增殖作用的表现都很重要。