DNA binding of sunitinib: Spectroscopic evidence via circular dichroism and nuclear magnetic resonance

Eszter Kiss, Arash Mirzahosseini, Ágnes Hubert, A. Ambrus, L. Őrfi, P. Horváth

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Sunitinib is a non-selective tyrosine kinase inhibitor, but in its chemical structure there can be discovered certain features, which suggest the ability to bind to DNA. These elements are the planar aromatic system and the tertiary amine function, which is protonated at the pH of the organism. In this study, the binding of the drug sunitinib to DNA was investigated using circular dichroism (CD), 1H NMR and UV spectroscopies, along with CD melting. For these studies DNA was isolated from calf thymus (CT), salmon fish sperm (SS), and chicken erythrocyte (CE), however for our purposes an artificially constructed and highly purified plasmid DNA (pUC18) preparation proved to be the most suitable. DNA binding of the drug was confirmed by shifts in the characteristic CD bands of the DNA, the appearance of an induced CD (ICD) signal in the upper absorption region of sunitinib (300 nm–500 nm), and the evidence from CD melting studies and the NMR. Based on the CD and NMR measurements, it can be assumed that sunitinib has a multiple-step binding mechanism.

Original languageEnglish
Pages (from-to)355-361
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume150
DOIs
Publication statusPublished - Feb 20 2018

Fingerprint

Circular Dichroism
Magnetic Resonance Spectroscopy
Nuclear magnetic resonance
DNA
Freezing
Melting
Thymus
Salmon
Ultraviolet spectroscopy
Pharmaceutical Preparations
Protein-Tyrosine Kinases
Fish
Thymus Gland
Nuclear magnetic resonance spectroscopy
Amines
Spermatozoa
sunitinib
Chickens
Fishes
Plasmids

Keywords

  • 1H NMR
  • Circular dichroism
  • DNA
  • Induced circular dichroism
  • Stauration transfer
  • Sunitinib

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

DNA binding of sunitinib : Spectroscopic evidence via circular dichroism and nuclear magnetic resonance. / Kiss, Eszter; Mirzahosseini, Arash; Hubert, Ágnes; Ambrus, A.; Őrfi, L.; Horváth, P.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 150, 20.02.2018, p. 355-361.

Research output: Contribution to journalArticle

@article{13a73ecc3cd04ca3b4ad84d69c4342b9,
title = "DNA binding of sunitinib: Spectroscopic evidence via circular dichroism and nuclear magnetic resonance",
abstract = "Sunitinib is a non-selective tyrosine kinase inhibitor, but in its chemical structure there can be discovered certain features, which suggest the ability to bind to DNA. These elements are the planar aromatic system and the tertiary amine function, which is protonated at the pH of the organism. In this study, the binding of the drug sunitinib to DNA was investigated using circular dichroism (CD), 1H NMR and UV spectroscopies, along with CD melting. For these studies DNA was isolated from calf thymus (CT), salmon fish sperm (SS), and chicken erythrocyte (CE), however for our purposes an artificially constructed and highly purified plasmid DNA (pUC18) preparation proved to be the most suitable. DNA binding of the drug was confirmed by shifts in the characteristic CD bands of the DNA, the appearance of an induced CD (ICD) signal in the upper absorption region of sunitinib (300 nm–500 nm), and the evidence from CD melting studies and the NMR. Based on the CD and NMR measurements, it can be assumed that sunitinib has a multiple-step binding mechanism.",
keywords = "1H NMR, Circular dichroism, DNA, Induced circular dichroism, Stauration transfer, Sunitinib",
author = "Eszter Kiss and Arash Mirzahosseini and {\'A}gnes Hubert and A. Ambrus and L. Őrfi and P. Horv{\'a}th",
year = "2018",
month = "2",
day = "20",
doi = "10.1016/j.jpba.2017.12.004",
language = "English",
volume = "150",
pages = "355--361",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",

}

TY - JOUR

T1 - DNA binding of sunitinib

T2 - Spectroscopic evidence via circular dichroism and nuclear magnetic resonance

AU - Kiss, Eszter

AU - Mirzahosseini, Arash

AU - Hubert, Ágnes

AU - Ambrus, A.

AU - Őrfi, L.

AU - Horváth, P.

PY - 2018/2/20

Y1 - 2018/2/20

N2 - Sunitinib is a non-selective tyrosine kinase inhibitor, but in its chemical structure there can be discovered certain features, which suggest the ability to bind to DNA. These elements are the planar aromatic system and the tertiary amine function, which is protonated at the pH of the organism. In this study, the binding of the drug sunitinib to DNA was investigated using circular dichroism (CD), 1H NMR and UV spectroscopies, along with CD melting. For these studies DNA was isolated from calf thymus (CT), salmon fish sperm (SS), and chicken erythrocyte (CE), however for our purposes an artificially constructed and highly purified plasmid DNA (pUC18) preparation proved to be the most suitable. DNA binding of the drug was confirmed by shifts in the characteristic CD bands of the DNA, the appearance of an induced CD (ICD) signal in the upper absorption region of sunitinib (300 nm–500 nm), and the evidence from CD melting studies and the NMR. Based on the CD and NMR measurements, it can be assumed that sunitinib has a multiple-step binding mechanism.

AB - Sunitinib is a non-selective tyrosine kinase inhibitor, but in its chemical structure there can be discovered certain features, which suggest the ability to bind to DNA. These elements are the planar aromatic system and the tertiary amine function, which is protonated at the pH of the organism. In this study, the binding of the drug sunitinib to DNA was investigated using circular dichroism (CD), 1H NMR and UV spectroscopies, along with CD melting. For these studies DNA was isolated from calf thymus (CT), salmon fish sperm (SS), and chicken erythrocyte (CE), however for our purposes an artificially constructed and highly purified plasmid DNA (pUC18) preparation proved to be the most suitable. DNA binding of the drug was confirmed by shifts in the characteristic CD bands of the DNA, the appearance of an induced CD (ICD) signal in the upper absorption region of sunitinib (300 nm–500 nm), and the evidence from CD melting studies and the NMR. Based on the CD and NMR measurements, it can be assumed that sunitinib has a multiple-step binding mechanism.

KW - 1H NMR

KW - Circular dichroism

KW - DNA

KW - Induced circular dichroism

KW - Stauration transfer

KW - Sunitinib

UR - http://www.scopus.com/inward/record.url?scp=85039157151&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039157151&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2017.12.004

DO - 10.1016/j.jpba.2017.12.004

M3 - Article

C2 - 29287262

AN - SCOPUS:85039157151

VL - 150

SP - 355

EP - 361

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -