Construction of polyamine-modified uridine and adenosine derivatives--evaluation of DNA binding capacity and cytotoxicity in vitro.
We here report the synthesis of the two polyamine-based nucleoside derivatives 5-{[bis-(3-aminopropyl)amino]acetamido-1-propynyl}uridine and 2-{[bis-(3-aminopropyl)amino]-acetamido-1-propynyl}adenosine. The various polyamine derivatives have been used in thermal melting analysis using DNA from herring testes, and in cellular studies using four different cell lines. The compounds were all found to be non-toxic, thus holding good promise for future use as siRNA building blocks.
Ghatnekar
Johannes
J
Organic Chemistry, Chemical Center, Lund Univesity, PO Box 124, SE-22100 Lund, Sweden.
Hägerlöf
Margareta
M
Oredsson
Stina
S
Alm
Kersti
K
Elmroth
Sofi K C
SK
Persson
Tina
T
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism / Q000379:methods; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013696:Temperature; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
C525627:5-((bis-(3-aminopropyl)amino)acetamido-1-propynyl)adenosine; C525628:5-((bis-(3-aminopropyl)amino)acetamido-1-propynyl)uridine; D011073:Polyamines; D004247:DNA; D000241:Adenosine; D014529:Uridine