Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy

Susan J. Berners-Price; Luca Ronconi; Peter J. Sadler

doi:10.1016/j.pnmrs.2006.05.002

Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy

Susan J. Berners-Price, Luca Ronconi, Peter J. Sadler

Research output: Contribution to a Journal (Peer & Non Peer) › Review article › peer-review

175 Citations (Scopus)

Abstract

The kinetics and mechanism of DNA platinization reactions with the detection of platinization sites on proteins and studies of new platinum drugs under investigation are discussed. Both Pt(II) and Pt(IV) are diamagnetic and so their complexes give relatively sharp NMR peak. Pt NMR resonances with their very wide range of chemical shifts can usually be observed from solutions with millimolar concentrations of complexes. In order to gain an understanding of the chemical reactivity of the cis-(PtCl₂(NH₃)(2-pic)), its crystal structure and hydrolysis behavior have been investigated. Analysis of the rate constants for the stepwise formation of the intrastrand cross-links shows that the aquation of cisplatin is slowed by 30-40% in the presence of the DNA. Platinum anticancer drugs are now widely used in the clinic for the treatment of cancer and much effort is currently directed at designing new platinum drugs which offer a wider spectrum of activity.

Original language	English
Pages (from-to)	65-98
Number of pages	34
Journal	Progress in Nuclear Magnetic Resonance Spectroscopy
Volume	49
Issue number	1
DOIs	https://doi.org/10.1016/j.pnmrs.2006.05.002
Publication status	Published - 15 Aug 2006
Externally published	Yes

Keywords

Aquation
DNA
Glutathione
Kinetics
N NMR
NMR
Platinum drugs
Proteins
Pt NMR
[H,N] NMR

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.pnmrs.2006.05.002

Cite this

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title = "Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy",

abstract = "The kinetics and mechanism of DNA platinization reactions with the detection of platinization sites on proteins and studies of new platinum drugs under investigation are discussed. Both Pt(II) and Pt(IV) are diamagnetic and so their complexes give relatively sharp NMR peak. Pt NMR resonances with their very wide range of chemical shifts can usually be observed from solutions with millimolar concentrations of complexes. In order to gain an understanding of the chemical reactivity of the cis-(PtCl2(NH3)(2-pic)), its crystal structure and hydrolysis behavior have been investigated. Analysis of the rate constants for the stepwise formation of the intrastrand cross-links shows that the aquation of cisplatin is slowed by 30-40\% in the presence of the DNA. Platinum anticancer drugs are now widely used in the clinic for the treatment of cancer and much effort is currently directed at designing new platinum drugs which offer a wider spectrum of activity.",

keywords = "Aquation, DNA, Glutathione, Kinetics, N NMR, NMR, Platinum drugs, Proteins, Pt NMR, [H,N] NMR",

author = "Berners-Price, \{Susan J.\} and Luca Ronconi and Sadler, \{Peter J.\}",

year = "2006",

month = aug,

day = "15",

doi = "10.1016/j.pnmrs.2006.05.002",

language = "English",

volume = "49",

pages = "65--98",

journal = "Progress in Nuclear Magnetic Resonance Spectroscopy",

issn = "0079-6565",

publisher = "Elsevier B.V.",

number = "1",

}

TY - JOUR

T1 - Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy

AU - Berners-Price, Susan J.

AU - Ronconi, Luca

AU - Sadler, Peter J.

PY - 2006/8/15

Y1 - 2006/8/15

N2 - The kinetics and mechanism of DNA platinization reactions with the detection of platinization sites on proteins and studies of new platinum drugs under investigation are discussed. Both Pt(II) and Pt(IV) are diamagnetic and so their complexes give relatively sharp NMR peak. Pt NMR resonances with their very wide range of chemical shifts can usually be observed from solutions with millimolar concentrations of complexes. In order to gain an understanding of the chemical reactivity of the cis-(PtCl2(NH3)(2-pic)), its crystal structure and hydrolysis behavior have been investigated. Analysis of the rate constants for the stepwise formation of the intrastrand cross-links shows that the aquation of cisplatin is slowed by 30-40% in the presence of the DNA. Platinum anticancer drugs are now widely used in the clinic for the treatment of cancer and much effort is currently directed at designing new platinum drugs which offer a wider spectrum of activity.

AB - The kinetics and mechanism of DNA platinization reactions with the detection of platinization sites on proteins and studies of new platinum drugs under investigation are discussed. Both Pt(II) and Pt(IV) are diamagnetic and so their complexes give relatively sharp NMR peak. Pt NMR resonances with their very wide range of chemical shifts can usually be observed from solutions with millimolar concentrations of complexes. In order to gain an understanding of the chemical reactivity of the cis-(PtCl2(NH3)(2-pic)), its crystal structure and hydrolysis behavior have been investigated. Analysis of the rate constants for the stepwise formation of the intrastrand cross-links shows that the aquation of cisplatin is slowed by 30-40% in the presence of the DNA. Platinum anticancer drugs are now widely used in the clinic for the treatment of cancer and much effort is currently directed at designing new platinum drugs which offer a wider spectrum of activity.

KW - Aquation

KW - DNA

KW - Glutathione

KW - Kinetics

KW - N NMR

KW - NMR

KW - Platinum drugs

KW - Proteins

KW - Pt NMR

KW - [H,N] NMR

UR - https://www.scopus.com/pages/publications/33748102436

U2 - 10.1016/j.pnmrs.2006.05.002

DO - 10.1016/j.pnmrs.2006.05.002

M3 - Review article

SN - 0079-6565

VL - 49

SP - 65

EP - 98

JO - Progress in Nuclear Magnetic Resonance Spectroscopy

JF - Progress in Nuclear Magnetic Resonance Spectroscopy

IS - 1

ER -

Insights into the mechanism of action of platinum anticancer drugs from multinuclear NMR spectroscopy

Abstract

Keywords

UN SDGs

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