Zhu T, Wei Z, Tung C H, Dickerhof W A, Breslauer K J, Georgopoulos D E, Leibowitz M J, Stein S
Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854.
Antisense Res Dev. 1993 Fall;3(3):265-75. doi: 10.1089/ard.1993.3.265.
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.
