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Application of Metallomics and Metalloproteomics for Understanding the Molecular Mechanisms of Action of Metal-Based Drugs

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Essential and Non-essential Metals

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

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Abstract

Metals play a significant role in biological processes, and metal-based drugs nowadays have been commonly used for therapeutic and diagnostic purposes. However, due to severe side effects with metallodrugs and acquired drug resistance, more metallodrugs are being developed, with improved pharmacological profiles and less side effects. With the rapid development of metallomic strategies in understanding metals in complex biological systems, their successful application in the field of medicinal inorganic chemistry has led to significant progresses in understanding the mechanisms of actions of metal-based drugs. This chapter introduces the concepts and research techniques in metallomics and metalloproteomics and expatiates the fate of metal-based drugs as well as metallic nanoparticles in biological systems revealed by metallomic studies.

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Abbreviations

16HBE:

Normal bronchial epithelial cells

2D-GE:

Two-dimensional gel electrophoresis

A549:

Human alveolar adenocarcinoma epithelial cells

APL:

Acute promyelocytic leukemia

ATO:

Arsenic trioxide

Au NRs:

Au nanorods

CBS:

Colloidal bismuth subcitrate

CE:

Capillary electrophoresis

ESI-MS:

Electrospray ionization mass spectrometry

GE-ICP-MS:

Online coupling of column-type gel electrophoresis with inductively coupled plasma-mass spectrometry

GO:

Gene ontology

H. pylori :

Helicobacter pylori

HF5:

Hollow fiber flow field-flow fractionation

HSAB:

Hard-soft acid-base

ICP-MS:

Inductively coupled plasma-mass spectrometry

ICP-TOF-MS:

Inductively coupled plasma time-of-flight mass spectrometry

IEC:

Ion-exchange chromatography

IEF:

Isoelectric focusing

IMAC:

Immobilized metal affinity chromatography

KP1019:

Trans-[Ru(III)(Ind)2Cl4][IndH]

LA-12:

(OC-6-43)-bis(acetato) (1-adamantylamine) amminedichloroplatinum (IV)

LA-ICP-MS:

Laser ablation-inductively coupled plasma-mass spectrometry

LoVo:

Human colon carcinoma cell line

MALDI-TOF-MS:

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

MAPK:

Mitogen-activated protein kinase

MRP:

Multidrug resistance protein

MS/MS:

Tandem mass spectrometry

MudPIT:

Multidimensional protein identification

NAMI-A:

Trans-[Ru(III)(dmso)(Im)Cl4][ImH]

NanoSIMS:

Nanoscale secondary ion mass spectrometry

NPs:

Nanoparticles

PAK:

Protein kinase

pIs:

Isoelectric points

PMH:

Primary hepatocytes

PTA:

1,3,5-Triaza-7-phosphatricyclo-[3.3.1.1]decane

RBC:

Ranitidine bismuth citrate

RBP4:

Retinol-binding protein 4

RPLC:

Reversed-phase liquid chromatography

RPTECs:

Renal proximal tubule epithelial cells

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

SEC:

Size-exclusion chromatography

SELDI-TOF-MS:

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

SRIXE:

Synchrotron radiation-induced X-ray emission

SR-TXM:

Synchrotron radiation-beam transmission X-ray microscopy

SR-XANES:

SR-X-ray absorption near edge structure

SR-XRF:

Synchrotron radiation X-ray fluorescence

TEM:

Transmission electron microscopy

THP-1:

Human monocyte

WHO:

World Health Organization

XAS:

X-ray absorption spectroscopy

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Acknowledgments

This work was supported by the Research Grants Council of Hong Kong (HKU704612, HKU703913, HKU17304614, HKU17305415), the University of Hong Kong (for an e-SRT on Integrative Biology), and the “Thousand Talents Program” start-up fund and a “Young Teacher Training Program” fund from Sun Yat-Sen University. HB Wang is acknowledged for a Hong Kong PhD Fellowship (HKPF).

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Authors and Affiliations

  1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen Unviersity, Guangzhou, 510275, China

    Yuchuan Wang & Hongzhe Sun

  2. Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China

    Haibo Wang, Hongyan Li & Hongzhe Sun

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  1. Yuchuan Wang
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  2. Haibo Wang
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  3. Hongyan Li
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  4. Hongzhe Sun
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Correspondence to Hongzhe Sun .

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  1. Natl Ctr Envtl Assessment Office of Res and Devt, Research Triangle Park, North Carolina, USA

    Anuradha Mudipalli

  2. Professor of Environmental Medicine, New York University, Tuxedo, New York, USA

    Judith T. Zelikoff

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Wang, Y., Wang, H., Li, H., Sun, H. (2017). Application of Metallomics and Metalloproteomics for Understanding the Molecular Mechanisms of Action of Metal-Based Drugs. In: Mudipalli, A., Zelikoff, J. (eds) Essential and Non-essential Metals. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-55448-8_9

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