Metals in medicine
Metals in medicine

Start this free course now. Just create an account and sign in. Enrol and complete the course for a free statement of participation or digital badge if available.

Free course

Metals in medicine

5.3 Platinum binding to DNA

Oligonucleotides are short sections of DNA (2 to 15 nucleotides long) used for model studies. They are often referred to as a ‘duplex’ in recognition of the two-stranded helical structure of DNA.

The early structural characterisation of oligonucleotide-bound cisplatin was done using X-ray crystallography, cap h one postfix times cap n times cap m times cap r and molecular modelling. Cisplatin was found to form a cis complex with two adjacent guanines on the same strand (known as a G(N7)–p–G(N7) linkage, often shortened to G–p–G or G–G). This is shown in Figure 19.

Active content not displayed. This content requires JavaScript to be enabled.
Figure 19  NMR structure of the DNA duplex dodecamer d(CCTCTG*G*TCTCC). d(GGAGACCAGAGG), containing the cisplatin (GpG–N7(1), N7(2)) 1,2-intrastrand cross-link at the position of the asterisks (pdb 1A84 [Tip: hold Ctrl and click a link to open it in a new tab. (Hide tip)] ; Gelasco and Lippard, 1998).
Interactive feature not available in single page view (see it in standard view).

Experiments found that cisplatin formed several different types of adduct with the DNA oligomers.

The major product (60–65%) is the G–G 1,2-intrastrand link between guanine residues which reside in the major groove in the B-form DNA (also shown in Figure 20): cis-[Pt(NH3)2(G–p–G)] (Structure 6).

Smaller quantities of other adducts include:

  • 20–25% of a G–A 1,2-intrastrand: cis-[Pt(NH3)2(A–p–G)], (Structure 7).
    Structure 6 (left) and 7 (right)
  • 5–10% of more widely spaced guanine adducts: the 1,3-intrastrand and G–p–G interstrand complexes (Structure 8, 9 and Figure 20). (Note: N in Structure 8 represents another base.) In the latter, cisplatin forms a cross-link between the two strands.
    Structure 8 (left) and 9 (right)
Active content not displayed. This content requires JavaScript to be enabled.
Figure 20  NMR solution structure of the short duplex [d(CAT–AG*CTATG)]2 cross-linked at the position of the asterisk which here is doubled to represent guanine bases on two strands (pdb 1DDP; Huang et al., 1995).
Interactive feature not available in single page view (see it in standard view).
  • 2–5% of a monoadduct (Structure 10), and < 1% of DNA–protein binding (Structure 11).
    Structure 10 (left) and 11 (right)

Take your learning further

Making the decision to study can be a big step, which is why you'll want a trusted University. The Open University has 50 years’ experience delivering flexible learning and 170,000 students are studying with us right now. Take a look at all Open University courses.

If you are new to University-level study, we offer two introductory routes to our qualifications. You could either choose to start with an Access module, or a module which allows you to count your previous learning towards an Open University qualification. Read our guide on Where to take your learning next for more information.

Not ready for formal University study? Then browse over 1000 free courses on OpenLearn and sign up to our newsletter to hear about new free courses as they are released.

Every year, thousands of students decide to study with The Open University. With over 120 qualifications, we’ve got the right course for you.

Request an Open University prospectus371