Synthesis of antisense oligonucleotide-peptide conjugate targeting to GLUT-1 in HepG-2 and MCF-7 Cells.
A simple procedure for the preparation of oligonucleotide-peptide conjugate was developed. p-Hydroxy-benzoic acid was used as a linker for the connection of the fragments of peptide and oligonucleotide. It was found that such formed linkage was stable under the conditions of conjugate synthesis. The designed conjugate targeting to GLUT-1 showed up to 50% inhibition of cell proliferation in HepG-2 and MCF-7 cells. Comparing to the results from the expressed antisense RNA in cancer cells, it was proposed that the conjugate of signal peptide mimic and antisense oligonucleotide could improve the permeability of antisense oligonucleotide through cell membrane.
Chen
Chang-Po
CP
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Li
Xiao-Xu
XX
Zhang
Liang-Ren
LR
Min
Ji-Mei
JM
Chan
Judy Yuet-Wah
JY
Fung
Kwok-Pui
KP
Wang
Sheng-Qi
SQ
Zhang
Li-He
LH
D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D051272:Glucose Transporter Type 1; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000494:pharmacology; D010226:Parabens / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013873:Thionucleotides; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003432:Cross-Linking Reagents; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D016376:Oligonucleotides, Antisense; D010226:Parabens; D010455:Peptides; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D013873:Thionucleotides; C038193:4-hydroxybenzoic acid