Family of hemorphins: co-relations between amino acid sequences and effects in cell cultures.
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.
Blishchenko
Elena Y
EY
Group of Protein Research, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, Moscow, Russia. karelin@ibch.siobc.ras.ru
Sazonova
Olga V
OV
Kalinina
Olga A
OA
Yatskin
Oleg N
ON
Philippova
Marina M
MM
Surovoy
Andrei Y
AY
Karelin
Andrei A
AA
Ivanov
Vadim T
VT
D000595:Amino Acid Sequence; D000818:Animals; D006454:Hemoglobins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D006454:Hemoglobins; C070564:LVV-hemorphin 6; D010446:Peptide Fragments; C094394:VV-hemorphin-7