Solid-Phase Synthesis of a Monofunctional trans-a2PtII Complex Tethered to a Single-Stranded Oligonucleotide

Abstract

Cross-linking ability is possible with the oligonucleotide-tethered, monofunctional trans-Pt(II) complex shown. It was synthesized by a novel solid-phase approach comprising conjugation of immobilized tetrathymidylic acid with a trans-a(2)Pt(II) building unit, ammonolysis, and transformation of the resulting complex (R=1-N-cyclohexylmethylthyminate) into the chloro derivative (R=Cl). a=NH(2)CH(3), T=thymine.

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“…48 The 5A-hydroxy function of a supportbound ODN can also be activated with 2-cyanoethyl-N,N-diisopropylphosphorochloridite, and a hydroxy group containing conjugate group can then be attached as a phosphite ester, followed by oxidation to a phosphate ester. 49 Several conjugate groups have been tethered to the 3A-end of the ODN chain by making use of appropriately modified linkers. For example, a tetraphenylporphyrin conjugate has been prepared on a N a -Fmoc-N e -(4-methyltrityl)lysine linker esterified to a hydroxy derivatized Tenta Gel.…”

A Click Chemistry Approach to Targeted DNA Crosslinking with cis‐Platinum(II)‐Modified Triplex‐Forming Oligonucleotides

“…[10] Here, a single labile trans site on the probe‐bound Pt II complex is available to crosslink with a purine base on the target duplex. Although mono‐functional Pt II ‐TFOs have previously been generated through platinum‐derivatised phosphoramidites [11] and solid‐phase synthesis of tethered trans ‐Pt II motifs, [12] surprisingly little research has been carried out to extend this concept towards the construction of bifunctional cisplatin(II)‐TFO motifs. Further attempts to incorporate platinated nucleotide building blocks into oligonucleotides (ON) using solid‐phase synthesis have yielded inactive platinum products, [13] although a cis ‐platinum(II)‐tethered ON was shown to retain crosslinking ability and displayed adduct formation against a 25:29‐mer duplex target (Figure S‐1).…”

Triplex mediated delivery of a platinum complex to a specific DNA target site

“…However, there are only a few reports in the literature describing the synthesis of platinated oligonucleotides, and those often involve a trans-a 2 Pt II species (a ¼ NH 3 or amine) [30][31][32][33], although the preparation of cis derivatives is also known [34]. The synthesis of platinated DNA sequences via the reaction of the oligonucleotide with a Pt II species does not proceed regio-selectively and results in a complicated mixture of end products.…”