Oligonucleotide-poly-L-ornithine conjugates: binding to complementary DNA and RNA.
On the basis of the reported enhanced antisense activity of polylysine-oligonucleotide conjugates, a synthetic 12-mer oligodeoxyribonucleotide has been coupled at its 5' terminus to a series of positively charged (delta-ornithine)n cysteine peptides. Binding between the nucleic acid-peptide conjugate and its complementary DNA target sequence was detected by the impact of complexation on the melting temperature (Tm). It was found that the Tm for the nucleic acid-peptide gradually increased with increasing net charge on the conjugated peptide. Site-directed cleavage with RNase H demonstrates that the peptide-modified oligomer also hybridizes with its RNA target sequence. Increased affinity for target mRNA with net charge was shown by a cell-free translation arrest assay.
Zhu
T
T
Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854.
Wei
Z
Z
Tung
C H
CH
Dickerhof
W A
WA
Breslauer
K J
KJ
Georgopoulos
D E
DE
Leibowitz
M J
MJ
Stein
S
S
D001483:Base Sequence; D018076:DNA, Complementary / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011107:Polylysine / Q000378:metabolism; D014176:Protein Biosynthesis; D018075:RNA, Complementary / Q000378:metabolism*; D016914:Ribonuclease H / Q000378:metabolism; D014158:Transcription, Genetic
D018076:DNA, Complementary; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D010455:Peptides; D018075:RNA, Complementary; C008973:polyornithine; D011107:Polylysine; D016914:Ribonuclease H