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Peptide Engineering Approach to Introduce an Improved Calcitonin Mutant

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Abstract

Calcitonin is a 32-amino acid peptide, which causes a decrease in blood calcium levels and bone resorption in the human body. It is produced in different species. Salmon calcitonin is used as a medicine for diseases such as osteoporosis, Paget’s disease, and hypercalcemia. However, the salmon calcitonin peptide used as a medicine, could induce immune responses in humans. Decreasing the antigenicity of salmon calcitonin could improve this molecule for pharmaceutical usage. In this study, improving physicochemical properties and reducing allergenicity and especially the antigenicity of salmon calcitonin were followed. The calcitonin sequences of different species were evaluated, and those with better properties were considered as a guide for peptide engineering. In silico methods were utilized to characterize the properties of the reviewed calcitonin sequences, and the best sequences (the calcitonin of sheep, dog, rat, and human) were used as a template to decrease the antigenicity of salmon calcitonin. The epitopic parts, i.e., amino acids 16 to 29, were identified by different servers. Hot spot residues including Y22, N26, T27, and S29 were characterized based on the main criteria of being a B-cell epitope including convexity index, hydrophilicity, and surface accessibility. These residues were replaced with lower antigenic counterparts. Results showed the final selected mutant (T27V/S29V) had a lower antigenicity and higher solubility and stability than salmon calcitonin. Thus, our suggested mutant could be a potential alternative candidate to salmon calcitonin. However, future in vitro and in vivo evaluations are needed to confirm its suitability for clinical usage.

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ACKNOWLEDGMENTS

The authors would like to thank the Research Council of Shiraz University of Medical Sciences, Shiraz University of Medical Sciences in Iran for supporting this research.

Funding

This work was supported by ongoing institutional funding. No additional grants to carry out or direct this particular research were obtained.

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Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    M. Zarei, B. Abedini, A. Dehshahri & M. Negahdaripour

  2. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    M. Zarei, B. Abedini, A. Dehshahri & M. Negahdaripour

  3. Computational Vaccine and Drug Design Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    M. Negahdaripour

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  1. M. Zarei
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  2. B. Abedini
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M. Zarei and B. Abedini contributed equally to this manuscript.

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Correspondence to M. Negahdaripour.

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Zarei, M., Abedini, B., Dehshahri, A. et al. Peptide Engineering Approach to Introduce an Improved Calcitonin Mutant. Mol Biol (2024). https://doi.org/10.1134/S0026893324700110

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