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2000
Volume 25, Issue 5
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

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 anti-cancer agents.

© 2025 Bentham Science Publishers
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2024-10-18
2025-12-27

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Evolutionary Sequences and Structural Information-driven Reconstruction of New Insulin-like Growth Factor-I Peptide Variants
Current Molecular Medicine 25, 652 (2025); https://doi.org/10.2174/0115665240333309241010123744
/content/journals/cmm/10.2174/0115665240333309241010123744
/content/journals/cmm/10.2174/0115665240333309241010123744
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  • Article Type:     Research Article
Keyword(s): ASR; cancer; Homo sapiens; IGF-IR; insulin; Insulin-like growth factor-I

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