Monatshefte für Chemie - Chemical Monthly

, Volume 150, Issue 12, pp 2061–2070 | Cite as

Biophysical and computational approaches to unravel the molecular interaction mechanism of bromodeoxyuridine, a proliferative marker with human serum albumin

  • Amira Adlin Roslan
  • Salanee Kandandapani
  • Nor Farrah Wahidah Ridzwan
  • Saharuddin B. Mohamad
  • Saad TayyabEmail author
Original Paper


The interaction of a nucleoside analogue bromodeoxyuridine (BrdU) with human serum albumin (HSA) was studied to investigate the binding phenomenon and analyse the protein conformation upon BrdU binding. Multiple spectroscopic techniques, viz. intrinsic and 3-D fluorescence, UV–Vis absorption, and circular dichroism (CD) spectroscopy along with molecular docking were used. Decrease in the Stern–Volmer constant (Ksv) as well as the association constant (Ka) with increase in temperature suggested BrdU–HSA complex formation. Intermediate binding affinity between BrdU and HSA was evident from the Ka values (2.49–3.97 × 104 mol–1 dm3), while BrdU–HSA complex formation was driven by hydrophobic and van der Waals interactions along with hydrogen bonds, as revealed by thermodynamic data (ΔS = + 28.48 J mol−1 K−1; ΔH = − 17.16 kJ mol−1). Minor changes occur in both secondary and tertiary structures as well as in the fluorophores’ microenvironment of HSA, as recognized from the CD spectral results in the far-UV and the near-UV regions and 3-D fluorescence spectra, respectively. Use of site markers (warfarin and indomethacin for site I; diazepam for site II) as well as docking results suggested BrdU binding to both site I (more preferred) and site II, located in subdomains IIA and IIIA, respectively, of HSA.

Graphic abstract


Bromodeoxyuridine Human serum albumin Drug–protein interaction Fluorescence quenching Molecular modelling 



This work was financially supported by the Frontier Science Research Cluster (FSRC) (FG025-17-AFR) approved by the Institut Pengurusan dan Pemantauan Penyelidikan, University of Malaya. We thank the Dean, Faculty of Science and the Head, Institute of Biological Sciences, University of Malaya, for providing necessary facilities to carry out this work.

Supplementary material

706_2019_2518_MOESM1_ESM.docx (171 kb)
Supplementary material 1 (DOCX 171 kb)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Amira Adlin Roslan
    • 1
  • Salanee Kandandapani
    • 1
  • Nor Farrah Wahidah Ridzwan
    • 2
  • Saharuddin B. Mohamad
    • 2
    • 3
  • Saad Tayyab
    • 1
    • 3
    Email author
  1. 1.Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia
  2. 2.Bioinformatics Programme, Institute of Biological Sciences, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia
  3. 3.Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and HealthcareUniversity of MalayaKuala LumpurMalaysia

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