Issue 12, 1998

Reactivity of transplatin-modified oligonucleotides in triple-helical DNA complexes

Abstract

The purpose of this work was to gain insight into the formation of interstrand cross-links in DNA triple helices resulting from the association between double-stranded DNAs and the complementary oligonucleotides containing a single transplatin monofunctional adduct either trans-[Pt(NH3)2(dG)Cl]+ or trans-[Pt(NH3)2(dC)Cl]+. Depending upon its location along the oligonucleotide, a platinated guanine residue increases or decreases the thermal stability of the platinated triplexes, as shown on model systems in which the transplatin monofunctional adduct was replaced by a diethylenetriamineplatinum(II) adduct. The interstrand cross-linking reaction has been studied in triplexes containing a single transplatin monofunctional adduct as a function of several parameters. The rate of closure of the monofunctional adduct into an interstrand cross-link depends upon the nature of the adduct but not strongly on its location along the Hoogsteen strand. The closure of trans-[Pt(NH3)2(dC)Cl]+ is faster than that of trans-[Pt(NH3)2(dG)Cl]+. Whereas the closure of trans-[Pt(NH3)2(dC)Cl]+is hardly affected by the presence of a high concentration of NaCl in the medium, the closure of trans-[Pt(NH3)2(dG)Cl]+ is largely slowed down. These results are discussed in the context of the potential use of the platinated oligonucleotides to modulate gene expression. Re′activite′ d'oligonucle′otides modifie′s par le transplatine dans des triples he′lices d'ADN. L'objectif de ce travail est d'e′lucider certains aspects de la re′action de formation d'adduits interbrins dans des triples he′lices d'ADN forme′es par l'association entre des doubles he′lices d'ADN et les oligonucle′otides comple′mentaires contenant un adduit monofonctionnel du transplatine, soit trans-[Pt(NH3)2(dG)Cl]+, soit trans-[Pt(NH3)2(dC)Cl]+. Selon sa position dans l'oligonucle′otide, une guanine platine′e augmente ou diminue la stabilite′ thermique des triples he′lices platine′es. Ceci a e′te′ montre′ à l'aide de modèles dans lesquels l'adduit monofonctionnel du transplatine est remplace′ par un adduit du die′thylènetriamineplatine(II). La re′action de formation d'adduits interbrins a e′te′ e′tudie′e dans des triplexes platine′s en fonction de plusieurs paramètres. La vitesse de formation de l'adduit interbrin à partir de l'adduit monofonctionnel de′pend de la nature de l'adduit mais peu de sa position dans le brin Hoogsteen. La re′action du trans-[Pt(NH3)2(dC)Cl]+ est plus rapide que celle du trans-[Pt(NH3)2(dG)Cl]+. La pre′sence d'une grande concentration de NaCl dans le milieu re′actionnel n'a presque aucun effet sur la re′action du trans-[Pt(NH3)2(dC)Cl]+, mais ralentit fortement la re′action du trans-[Pt(NH3)2(dG)Cl]+. Ces re′sultats sont discute′s dans le cadre de l'utilisation potentielle des oligonucle′otides platine′s pour moduler l'expression ge′nique.

Article information

Article type
Paper

New J. Chem., 1998,22, 1479-1483

Reactivity of transplatin-modified oligonucleotides in triple-helical DNA complexes

E. Bernal-Me′ndez, J. Sun, F. González-Vílchez and M. Leng, New J. Chem., 1998, 22, 1479 DOI: 10.1039/A804446E

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