Radiolabelling Pt-based quadruplex DNA binders via click chemistry

Rainbow Lo; Aatikah Majid; Gilbert O. Fruhwirth; Ramon Vilar

doi:10.1016/j.bmc.2022.117097

Radiolabelling Pt-based quadruplex DNA binders via click chemistry

Rainbow Lo, Aatikah Majid, Gilbert O. Fruhwirth^*, Ramon Vilar

^*Corresponding author for this work

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Guanine-rich sequences of DNA and RNA can fold into intramolecular tetra-helical assemblies known as G-quadruplexes (G4). Their formation in vivo has been associated to a range of biological functions and therefore they have been identified as potential drug targets. Consequently, a broad range of small molecules have been developed to target G4s. Amongst those are metal complexes with Schiff base ligands. Herein, we report the functionalisation of one of these well-established G4 DNA binders (based on a square planar platinum(II)-salphen complex) with two different radiolabelled complexes. An ¹¹¹In-conjugate was successfully used to assess its in vivo distribution in a mouse tumour model using single-photon emission computed tomography (SPECT) imaging. These studies highlighted the accumulation of this Pt-salphen-¹¹¹In conjugate in the tumour.

Original language	English
Article number	117097
Journal	Bioorganic and Medicinal Chemistry
Volume	76
DOIs	https://doi.org/10.1016/j.bmc.2022.117097
Publication status	Published - 15 Dec 2022

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10.1016/j.bmc.2022.117097

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title = "Radiolabelling Pt-based quadruplex DNA binders via click chemistry",

abstract = "Guanine-rich sequences of DNA and RNA can fold into intramolecular tetra-helical assemblies known as G-quadruplexes (G4). Their formation in vivo has been associated to a range of biological functions and therefore they have been identified as potential drug targets. Consequently, a broad range of small molecules have been developed to target G4s. Amongst those are metal complexes with Schiff base ligands. Herein, we report the functionalisation of one of these well-established G4 DNA binders (based on a square planar platinum(II)-salphen complex) with two different radiolabelled complexes. An 111In-conjugate was successfully used to assess its in vivo distribution in a mouse tumour model using single-photon emission computed tomography (SPECT) imaging. These studies highlighted the accumulation of this Pt-salphen-111In conjugate in the tumour.",

author = "Rainbow Lo and Aatikah Majid and Fruhwirth, {Gilbert O.} and Ramon Vilar",

note = "Funding Information: RL and AM were supported by the Engineering and Physical Sciences Research Council (EPSRC grants EP/L015226/1 and EP/S023232/1) through a studentship. Animal experiments were supported by a Cancer Research UK grant [C48390/A21153] to GOF. The authors received further support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas{\textquoteright} NHS Foundation Trust and King's College London; and the Wellcome/EPSRC Centre for Medical Engineering at King's College London [WT 203148/Z/16/Z]. This research was funded in whole, or in part, by the Wellcome Trust [WT203148/Z/16/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The views expressed are those of the authors and not necessarily those of the NIHR, the National Health Service or the Department of Health. Dr Fahad Al-Salemeel is acknowledged for technical assistance for in vivo experiments. Funding Information: RL and AM were supported by the Engineering and Physical Sciences Research Council (EPSRC grants EP/L015226/1 and EP/S023232/1) through a studentship. Animal experiments were supported by a Cancer Research UK grant [C48390/A21153] to GOF. The authors received further support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London; and the Wellcome/EPSRC Centre for Medical Engineering at King{\textquoteright}s College London [WT 203148/Z/16/Z]. This research was funded in whole, or in part, by the Wellcome Trust [WT203148/Z/16/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The views expressed are those of the authors and not necessarily those of the NIHR, the National Health Service or the Department of Health. Dr Fahad Al-Salemeel is acknowledged for technical assistance for in vivo experiments. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

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doi = "10.1016/j.bmc.2022.117097",

language = "English",

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T1 - Radiolabelling Pt-based quadruplex DNA binders via click chemistry

AU - Lo, Rainbow

AU - Majid, Aatikah

AU - Fruhwirth, Gilbert O.

AU - Vilar, Ramon

N1 - Funding Information: RL and AM were supported by the Engineering and Physical Sciences Research Council (EPSRC grants EP/L015226/1 and EP/S023232/1) through a studentship. Animal experiments were supported by a Cancer Research UK grant [C48390/A21153] to GOF. The authors received further support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London; and the Wellcome/EPSRC Centre for Medical Engineering at King's College London [WT 203148/Z/16/Z]. This research was funded in whole, or in part, by the Wellcome Trust [WT203148/Z/16/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The views expressed are those of the authors and not necessarily those of the NIHR, the National Health Service or the Department of Health. Dr Fahad Al-Salemeel is acknowledged for technical assistance for in vivo experiments. Funding Information: RL and AM were supported by the Engineering and Physical Sciences Research Council (EPSRC grants EP/L015226/1 and EP/S023232/1) through a studentship. Animal experiments were supported by a Cancer Research UK grant [C48390/A21153] to GOF. The authors received further support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London; and the Wellcome/EPSRC Centre for Medical Engineering at King’s College London [WT 203148/Z/16/Z]. This research was funded in whole, or in part, by the Wellcome Trust [WT203148/Z/16/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The views expressed are those of the authors and not necessarily those of the NIHR, the National Health Service or the Department of Health. Dr Fahad Al-Salemeel is acknowledged for technical assistance for in vivo experiments. Publisher Copyright: © 2022 The Author(s)

PY - 2022/12/15

Y1 - 2022/12/15

N2 - Guanine-rich sequences of DNA and RNA can fold into intramolecular tetra-helical assemblies known as G-quadruplexes (G4). Their formation in vivo has been associated to a range of biological functions and therefore they have been identified as potential drug targets. Consequently, a broad range of small molecules have been developed to target G4s. Amongst those are metal complexes with Schiff base ligands. Herein, we report the functionalisation of one of these well-established G4 DNA binders (based on a square planar platinum(II)-salphen complex) with two different radiolabelled complexes. An 111In-conjugate was successfully used to assess its in vivo distribution in a mouse tumour model using single-photon emission computed tomography (SPECT) imaging. These studies highlighted the accumulation of this Pt-salphen-111In conjugate in the tumour.

AB - Guanine-rich sequences of DNA and RNA can fold into intramolecular tetra-helical assemblies known as G-quadruplexes (G4). Their formation in vivo has been associated to a range of biological functions and therefore they have been identified as potential drug targets. Consequently, a broad range of small molecules have been developed to target G4s. Amongst those are metal complexes with Schiff base ligands. Herein, we report the functionalisation of one of these well-established G4 DNA binders (based on a square planar platinum(II)-salphen complex) with two different radiolabelled complexes. An 111In-conjugate was successfully used to assess its in vivo distribution in a mouse tumour model using single-photon emission computed tomography (SPECT) imaging. These studies highlighted the accumulation of this Pt-salphen-111In conjugate in the tumour.

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DO - 10.1016/j.bmc.2022.117097

M3 - Article

C2 - 36417789

AN - SCOPUS:85142152856

SN - 0968-0896

VL - 76

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

M1 - 117097

ER -

Radiolabelling Pt-based quadruplex DNA binders via click chemistry

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