[GnRH analogues containing SV-40 virus T-antigen nuclear localization sequence].
To improve the efficiency of anticancer drugs due to their delivery to intracellular targets a set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized. NLS was attached to the parent molecule via ε-amino group of D-Lysine in position 1 or 6 of peptide sequence using orthogonal protection strategy. The biological activity studies revealed that incorporation of NLS moiety significantly increases cytotoxic activity of palmitoyl-containing GnRH analogues in vitro. The influence of tested peptides on tumor cells does not accompanied by the destruction of cell membrane, as confirmed in experiments with normal fibroblasts, used as a control.
S V
SV
Burov
T V
TV
Iablokova
M Iu
MIu
Dorosh
E V
EV
Kriviziuk
A M
AM
Efremov
S V
SV
Orlov
D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D011966:Receptors, LHRH / Q000378:metabolism; D013539:Simian virus 40 / Q000737:chemistry / Q000378:metabolism*
D000957:Antigens, Viral, Tumor; D000970:Antineoplastic Agents; D004337:Drug Carriers; D019913:Nuclear Localization Signals; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone