Oligonucleotide platination

What do the kinetic studies of oligonucleotide platination indicate about the factors which control each step of the formation of the final diadducts ... 

Fig 43. Site-specific platination of oligonucleotides. Reproduced with permission from Ref. (152). Copyright 1996, American Chemical Society. 

Alguero, B. Lopez de la Osa, J. Gonzalez, C. Pedroso, E. Marchan, V. Grandas, A. Selective platination of modified oligonucleotides and duplex cross-links. Angew. Chem. Int. Ed. 2006, 45, 8194-8197. 

Although structural studies on various platinated oligonucleotides clearly demonstrate the preponderance of GG and AG adducts, they do... 

The experimental determination of the rate constants for the platination of different oligonucleotides has turned out to be rather difficult. To avoid the complicacy due to the CL hydrolysis of the dichloro species,... 

Tsang SC, Guo ZJ, Chen YK, Green MLH, Hill HAO, Hambley TW, Sadler PJ (1997) Immobilization of platinated and iodinated oligonucleotides on carbon nanotubes. Angew. Chem. Int. Ed. Engl. 36 2198-2200. 

The other conformational characteristics of d(GpG) are hardly changed upon the platination. The crystallization ofcis-Pt adducts with oligonucleotides has been proved to be very difficult and only recently a few X-ray structures have become available (see below). 

Figure 14. Principle of antisense strategy applying a platinated oligonucleotide.

Oligonucleotides containing intrastrand or interstrand cross-links are easily separated by this technique. Over a period of 50 h, in the platinated duplex 1, only interstrand cross-links between complementary guanine and cytosine residues in agreement with previous results [64], are detected. In the platinated duplex 2, which contains a [Pt(dien)(dG)]2+ adduct in the lower strand three base pairs away from the trans-[Pt(NH3)2(dG)Cl]+ adduct and on its 5 -side, both intrastrand and interstrand cross-links are detected. In the platinated duplex 3, which contains a [Pt(dien)(dG)]2+ adduct in the lower strand two base pairs away from the /ra v-[Pt(NH3)2(dG)Cl]+ adduct and on its 3 -side, mainly two kinds of interstrand cross-links are detected. In the platinated duplex 4, which contains two [Pt(dien)(dG)]2+ adducts, two kinds of interstrand crosslinks are formed, but in a different ratio to that in duplex 3. In duplexes 3 and 4, there is one interstrand cross-link between the complementary guanine and cytosine residues, and the other is between the guanine and an adenine residue located four or five base pairs away on the 3 -side of the guanine residue. 

The specific and irreversible binding of the platinated oligonucleotides on large molecular weight targets and in various media has been demonstrated in vitro by the arrest of AMV reverse transcriptase and protein synthesis and in HBL lOOrasl cells [73],... 

Since the work of Zamecnik and Stephenson in 1978, showing that a synthetic 13-mer complementary to the 3 - and 5 -terminal sequences of the Rous Sarcoma Virus 35S was able to inhibit virus production in infected chick embryo fibroblast cells [77][78], numerous studies have been done to demonstrate that in vivo oligonucleotides can bind to their complementary sequences in mRNAs or DNA and subsequently act on the cellular machinery. The purpose of this section is to present briefly the potential interest of the platinated oligonucleotides in the context of the antisense and antigene strategies (for a comprehensive view of the antisense and antigene strategies, see [79-83] and references herein). 

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