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Comparative evaluation of amphotericin B binding to the native and modified forms of rice lipid-transfer protein: a possible perspective on improving the drug-binding affinity and specificity

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Abstract

Plant non-specific lipid-transfer proteins (nsLTPs) are small basic proteins which transport phospholipids between different cell membranes. They are classified, based on their molecular weight, into two subfamilies: nsLTP1 (9 kDa) and nsLTP2 (7 kDa). These proteins have received an increasing research interest as efficient drug carriers in drug delivery systems. However, there have been few studies conducted on their drug-binding characteristics. The present study aims to comparatively evaluate binding of amphotericin B (AmB, an antifungal drug) to the native and modified forms of rice nsLTP1 and to assess possible applications in drug delivery methods. The LTP1 was purified and then interaction of AmB with the native and modified forms of protein was investigated with various spectroscopic methods. The results showed that the AmB–LTP binding is associated with quenching of the protein intrinsic fluorescence. Furthermore, as temperature of the medium increased, the stability of the AmB–native LTP complex decreased, whereas the stability of the AmB–modified LTP increased. Analysis of the thermodynamic parameters of the AmB–protein complexes and extrinsic fluorescence data indicated that the lysine modification caused a change in the intermolecular interactions between the protein and AmB as well as in the protein surface hydrophobicity (PSH). Furthermore, Dixon plot showed that AmB inhibits ANS binding especially in the AmB–modified RLTP binding. Findings of the current study highlighted the drug-binding characteristics of the modified form of LTP necessitating further studies to profoundly evaluate the characteristics of its mutant forms.

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Acknowledgments

The authors thank the staff of Research Council of Kermanshah University of Medical Sciences for the financial support of this investigation. The sponsor, however, had no direct involvement with this work.

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Authors and Affiliations

  1. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Shabnam Maghsoudi, Mohammad Reza Ashrafi-Kooshk, Seyyed Abolghasem Ghadami, Ali Mostafaie & Reza Khodarahmi

  2. Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohsen Shahlaei & Reza Khodarahmi

  3. Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran

    Sirous Ghobadi

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  1. Shabnam Maghsoudi
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  2. Mohammad Reza Ashrafi-Kooshk
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  5. Sirous Ghobadi
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Correspondence to Mohammad Reza Ashrafi-Kooshk or Reza Khodarahmi.

Additional information

This work was performed in partial fulfillment of the requirements for MSc of S. Maghsoudi, in Medical Biology Research Center (and Faculty of Pharmaceutical Sciences), Kermanshah University of Medical Sciences, Kermanshah, Iran

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Maghsoudi, S., Ashrafi-Kooshk, M.R., Shahlaei, M. et al. Comparative evaluation of amphotericin B binding to the native and modified forms of rice lipid-transfer protein: a possible perspective on improving the drug-binding affinity and specificity. J IRAN CHEM SOC 10, 937–950 (2013). https://doi.org/10.1007/s13738-013-0231-7

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