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Synthesis and Characterisation of Chickpea Peptides-Zinc Chelates Having ACE2 Inhibitory Activity

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Abstract

Tryptic hydrolysates of protein fractions obtained by the Osborne method from chickpea (Cicer arietinum L.) seeds interacted with zinc ions and the results of chelation were monitored by the Energy Dispersive X-Ray (EDX) technique. The glutelin hydrolysate (GluHyd) reacted with zinc ions and depicted a relatively higher zinc content. For this reason, the zinc complex of the glutelin hydrolysate (GluHyd-Zn) was studied deeper, and 11 peptides were identified in its more zinc-containing second fraction obtained after gel filtration. The peptide HKERVQLHIIPTAVGK showed a relatively higher chelating capacity (57.86 ± 2.14%). According to the result of the ICP-OS analysis, 1 mg peptide could chelate 381.61 ± 133.39 µg zinc, and the molar ratio of peptide-zinc was about 1:4. Spectral methods proved that side chain and C-termini carboxyl groups of the peptide mostly were involved in chelation and N atoms of amino side chains, imidazole group of histidine, and N-termini at some extents were occupied by the metal ions. Modeling of zinc-peptide interaction was done using Molecular Operating Environment (MOE) software. The results of the docking correlate with the experimental data.

ACE2 inhibitory effect of HKERVQLHIIPTAVGK-Zn complex (IC50 = 1.5 mg/mL) was better than that of HKERVQLHIIPTAVGK (IC50 = 2.2 mg/mL).

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Abbreviations

AlbHyd:

Albumin hydrolysate

GloHyd:

Globulin hydrolysate

GluHyd:

Glutelin hydrolysate

ProHyd:

Prolamin hydrolysate

AlbHyd-Zn:

Albumin hydrolysate-zinc complex

GloHyd-Zn:

Globulin hydrolysate-zinc complex

GluHyd-Zn:

Glutelin hydrolysate-zinc complex

ProHyd-Zn:

Prolamin hydrolysate-zinc complex

MOE:

Molecular Operating Environment

CPH:

Chickpea protein hydrolysate

CPH-Zn:

Chickpea protein hydrolysate-Zn complex

CPFs:

Chickpea protein fractions

EDX:

Energy Dispersive X-Ray

PAR:

4-(2-pyridylazo) resorcinol

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Acknowledgements

The work was supported by CAS-TWAS President’s Fellowship Program.

This work was Funded by the Xinjiang Uygur Autonomous Region Tianshan Yingcai-Leading Talents in Scientific and Technological Innovation (Grand No. 2022TSYCLJ0008), Scientific Report of Foreign Expert by the PIFI Fund of the Chinese Academy of Sciences for invited scientists, 2019VBA0013, Chinese Academy of Sciences President’s International Fellowship Initiative (Grant No. 2023VBB0005), and National Foreign Expert Program “Foreign Young Talent Program (Grant No. QN2022045004L). We also thank Soyib Bozorov, Oybek Tursunkulov, and Uchqun Ishimov for their technical support.

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Authors and Affiliations

  1. State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and the Key Laboratory of Chemistry of Plant Resources in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, PR China

    Nurkhodja Mukhamedov, Ahmidin Wali, Haji Akber Aisa & Abulimiti Yili

  2. University of Chinese Academy of Sciences, Beijing, 100039, PR China

    Nurkhodja Mukhamedov & Ansor Yashinov

  3. Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Tashkent, 100125, Uzbekistan

    Nurkhodja Mukhamedov, Akmal Asrorov, Ansor Yashinov, Muzaffar Kayumov & Sharafitdin Mirzaakhmedov

  4. Department of Natural Substances Chemistry, National University of Uzbekistan, Tashkent, 100174, Uzbekistan

    Akmal Asrorov

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Nurkhodja Mukhamedov, Akmal Asrorov, Sharafitdin Mirzaakhmedov, Haji Akber Aisa, and Abulimiti Yili wrote the main manuscript text. Ansor Yashinov and Ahmidin Wali conducted experiments of biological activity screening and ACE2 inhibitory activity test. Muzaffar Kayumov made molecular modelling of peptide-zinc interaction. All authors reviewed the manuscript.

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Correspondence to Abulimiti Yili.

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Mukhamedov, N., Asrorov, A., Yashinov, A. et al. Synthesis and Characterisation of Chickpea Peptides-Zinc Chelates Having ACE2 Inhibitory Activity. Protein J 42, 547–562 (2023). https://doi.org/10.1007/s10930-023-10133-5

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