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Updated: Jun 12, 2025

Identification of Functional Protein Regions Through Chimeric Protein Construction
Published on: January 8, 2019
Evolutionary Sequences and Structural Information-driven Reconstruction of New Insulin-like Growth Factor-I Peptide
Nazam Khan1, Maryam Althobiti1, Raj Kumar Chinnadurai2
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Kingdom of Saudi Arabia.
Background:
Insulin-like growth factor-I (IGF-I) is crucial in controlling cell growth, proliferation, and apoptosis. Its strong link to the development of cancers such as breast, prostate, lung, thyroid, and colorectal has positioned the IGF-1 signalling pathway as a promising target for novel cancer therapies. When activated, the IGF-1 receptor (IGF-1R) binds to IGF-I, playing a central role in promoting tumour cell growth and survival.
Methods:
In this study, we combined evolutionary sequences with structural and functional data of IGF-1 to reconstruct ancestral sequences and design novel IGF-1 peptide variants.
Results:
The insulin-like growth factor system exhibits a vast sequence diversity, yet it shares a similar structural topology with conserved three pairs of disulfide linkages. Our study reveals that IGF-1 is associated with the IGF system of cell surface receptors through protein-protein interactions. Reconstructed IGF-1 variants show similar structure fold to reported viral IGF-1 competitive antagonists.
Conclusion:
This new insight guides the design of novel natural IGF-1 mimic peptides. It enhances our understanding of IGF-1's functionality and opens new avenues for the development of therapeutic peptides and small molecules as anticancer agents.
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