Terminally L-modified oligonucleotides: pairing, stability and biological properties.
An oligodeoxynucleotide (ODN), capable of reducing the growth of human B lymphocytes carrying the t(14;18) chromosome translocation, was prepared in different 'chemical versions': unmodified phosphodiester, phosphorothioate and phosphodiester capped with L-2'-deoxycytidine. Their binding affinity to the complementary synthetic target was studied by the melting point assay. The ODNs, administered to DOHH2 cells, were compared for stability in the culture medium, cellular uptake, time course of the intact sequence concentration within the cell and ability to inhibit cell growth. The 5', 3'-L-capped derivative and the phosphorothioate had comparable potency, superior to that of the unmodified ODN, in agreement with the concentration of undegraded ODNs within the cell.
Tondelli
L
L
ICoCEA, CNR, Bologna Italy.
Garbesi
A
A
Morelli
S
S
Calastretti
A
A
Copreni
E
E
Gong
L
L
Nicolin
A
A
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003720:Densitometry; D004355:Drug Stability; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000473:pathology; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013696:Temperature; D013873:Thionucleotides / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D009841:Oligonucleotides; D013873:Thionucleotides