Chinese Journal of Applied Chemistry ›› 2017, Vol. 34 ›› Issue (10): 1150-1160.DOI: 10.11944/j.issn.1000-0518.2017.10.160473

• Orginal Article • Previous Articles     Next Articles

Synthesis of Two L-Histidine Amide Derivatives and the Interaction Mechanism with Human Serum Albumin

HE Weia,ZOU Jiajiaa,LU Dongweia,CHENG Huia,LIN Cuiwuab*()   

  1. aSchool of Chemistry and Chemical Engineering
    bGuangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development,Guangxi University,Nanning,Guangxi 530004,China
  • Received:2016-11-24 Accepted:2017-03-10 Published:2017-09-29 Online:2017-09-29
  • Contact: LIN Cuiwu
  • Supported by:
    Supported by the National Natural Science Foundation of China(No.21362001), the Guangxi Natural Science Foundation of China(No.2013GXNSFDA019005)

Abstract:

L-Histidine has excellent affinity for biological organism. Its derivatives by structural modification may possess high pharmacological activity and bio-availability. In this work, two L-histidineamide derivatives were designed and synthesized by the reaction of L-histidine with trans-cinnamic acid and p-methoxycinnamic acid. Their structures were characterized by infrared, mass spectrometry, and nuclear magnetic resonance. The interaction mechanism of derivatives and human serum albumin(HSA) was investigated by molecular operating environment(MOE) molecular docking, fluorescence spectroscopy, synchronous fluorescence spectroscopy(SFS) and ultraviolet-visible(UV-Vis) absorption spectroscopy. The results of MOE molecular docking shows that the two derivatives exist in the hydrophobic pocket of subdomain ⅡA(site Ⅰ) of HSA under the action of van der Waals force and hydrophobic effect, with the simulation binding energy are -13.82 and -16.25 kcal/mol, respectively. The fluorescence quenching results show that the derivatives can interact with HSA and form new ground-state complexes and the fluorescence quenching process is a static quenching procedure. The binding of HSA to derivatives driven by van der Waals force was found from the thermodynamic parameters, and the binding equilibrium constants at different temperatures(300 K, 305 K, and 310 K) are 1.773×104, 6.354×103, 1.260×103, 5.314×104, 4.614×103, 1.420×103, respectively. The SFS characterization shows that the secondary structure of HSA has been changed by derivatives. Combining the results of UV-Vis spectra, it is obviously that under physiological conditions in vitro, the interaction between derivatives with HSA produces static quenching and conformational effects to the internal fluorescence of HSA through van der Waals force, which is consistent with the prediction of molecular docking, thus providing a reference for the further development of histidine amide derivatives research.

Key words: L-histidineamide derivatives, spectrometry methodology, human serum albumin, molecular docking