A concise method for the preparation of peptide and arginine-rich peptide-conjugated antisense oligonucleotide.
Peptide-oligonucleotide conjugates were synthesized using two strategies: a mimetic signal peptide-conjugated oligonucleotide was assembled stepwise on CPG by using 2,2-dimethyl-3-hydroxypropionic acid as a linker. To solve the precipitation problem in the coupling reaction caused by the electrostatic interaction of arginine-rich peptides and oligonucleotide, oligonucleotides were absorbed on an anion-exchange resin, and then the on-resin fragment was applied for the conjugation with arginine-rich peptide. The peptide-antisense oligonucleotides showed permeability to the cell membrane of HepG-2 cells.
Chen
Chang-Po
CP
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Zhang
Liang-Ren
LR
Peng
Yue-Feng
YF
Wang
Xiao-Bo
XB
Wang
Sheng-Qi
SQ
Zhang
Li-He
LH
D001120:Arginine / Q000138:chemical synthesis* / Q000235:genetics; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000235:genetics; D010455:Peptides / Q000138:chemical synthesis* / Q000235:genetics
D016376:Oligonucleotides, Antisense; D010455:Peptides; D001120:Arginine