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Synthesis, Characterization, and Evaluation of Radiometal-Containing Peptide Nucleic Acids

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Peptide Nucleic Acids

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1050))

Abstract

Peptide nucleic acids (PNAs) have very attractive properties for applications in nuclear medicine. Because PNAs have high selectivity for DNA/RNA recognition, resistance to nuclease/protease degradation, and high thermal and radiolytic stabilities, PNA bioconjugates could transform the areas of diagnostic and therapeutic nuclear medicine. In this book chapter, we report on the current developments towards the preparation of radiometal-containing PNA constructs and summarize the protocols for labeling these probes with 99mTc, 111In, 64Cu, 90Y, and 177Lu.

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Abbreviations

A:

Adenine

Ac-GdAGG:

TetrapeptideN-acetyl-glycine-d-alanine-glycine-glycine

BFCA:

Bifunctional chelating agent

Bhoc:

Benzhydryloxycarbonyl

Bipy:

2,2′-bipyridine

Boc:

Di-tert-butyl dicarbonate

C:

Cytosine

Cbz:

Benzyloxycarbonyl

DIPEA:

Diisopropylethylamine

DMF:

Dimethylformamide

DOTA:

1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid

Dpa-N3:

2-azido-N,N-bis((pyridin-2-yl)methyl)ethanamine

DPA:

N,N-bis(2-picolyl)amine

DPAm:

N,N-bis(2-picolyl)amide

DTPA:

Diethylenetriaminepentaacetic acid

EDTA:

Ethylenediaminetetraacetic acid

Fmoc:

9-fluorenylmethyloxycarbonyl

G:

Guanine

GdAGG:

Tetrapeptide glycine-d-alanine-glycine-glycine

HATU:

2-(1H-7-azabenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluoro-phosphate

HCl:

Hydrochloric acid

HEPES:

2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid

HPLC:

High-performance liquid chromatography

ITLC:

Instant thin-layer chromatography

MAG3 :

S-acetylmercaptoacetyltriglycine

MAS3 :

S-acetylmercaptoacetyltriserine

PET:

Positron emission tomography

PBS:

Phosphate-buffered saline

PNA:

Peptide nucleic acid

PzDA:

N-(1-pyrazolyl)ethyl-ethane-1,2-diamine

SBTG2DAP:

N,N′-bis(S-benzoyl-thioglycoloyl)diaminopropanoate

SEC:

Size-exclusion chromatography

SPECT:

Single-photon emission computed tomography

T:

Thymine

TETA:

1,4,8,11-tetraazacyclotetradecane1,4,8,11-tetraacetic acid

TFA:

Trifluoroacetic acid

TIS:

Triisopropylsilane

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Acknowledgments

The Institute of Radiopharmautical Cancer Research at the Helmholtz-Zentrum Dresden-Rossendorf, the Swiss National Science Foundation (Professorship N° PP00P2_133568 and Research Grant N° 200021_129910 to G.G.), and the University of Zurich are gratefully acknowledged for their generous financial support. The authors thank Prof. Nils Metzler-Nolte, Prof. Jörg Steinbach, Dr. Hans-Jürgen Pietzsch, Dr. Ralf Bergmann, and Dr. Tanmaya Joshi for helpful discussions.

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Authors and Affiliations

  1. Institute of Radiopharmaceutical Cancer Research, Helmholtz- Zentrum Dresden-Rossendorf, Dresden, Germany

    Holger Stephan & Christian Foerster

  2. Institute of Inorganic Chemistry, University of Zurich, Zurich, Switzerland

    Gilles Gasser

Authors
  1. Holger Stephan
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  2. Christian Foerster
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  3. Gilles Gasser
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Editors and Affiliations

  1. Dept. Cellular & Molecular Medicine, University of Copenhagen Faculty of Health Sciences, Copenhagen N, Denmark

    Peter E Nielsen

  2. NIH NIDDK, Bethesda, USA

    Daniel H. Appella

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Stephan, H., Foerster, C., Gasser, G. (2014). Synthesis, Characterization, and Evaluation of Radiometal-Containing Peptide Nucleic Acids. In: Nielsen, P., Appella, D. (eds) Peptide Nucleic Acids. Methods in Molecular Biology, vol 1050. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-553-8_4

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  • DOI: https://doi.org/10.1007/978-1-62703-553-8_4

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