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Intriguing Cystine-Knot Miniproteins in Drug Design and Therapeutics

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Toxins and Drug Discovery

Part of the book series: Toxinology ((TOXI))

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Abstract

Cystine-knot miniproteins (CKMPs) are members of cystine-rich protein families, typically comprising of less than 50 amino acids, widespread among various living organisms, including toxins of venomous animals such as spiders, scorpions, and marine cone snails. They have a characteristic knotted structure formed by three intramolecular disulphide bonds which provide for remarkable stability against extreme temperature, pH, chemical denaturation, and proteolysis. Evolution over years has yielded in structural and functional diversity of CKMPs across different organisms performing functions such as defense or modulation of cell growth and development. These biological roles have found therapeutic relevance over years such as in chronic pain, heart, and neurodegenerative diseases. With advances in protein engineering, the robust knotted scaffold of CKMPs has been used in the field of drug design and therapeutics for developing novel protease inhibitors, integrin binders, anti-HIV compounds, growth factor mimetics, multiepitope vaccine, and much more. This chapter provides a brief overview of the CKMPs and provides glimpses on why they have become increasingly attractive in drug design and therapeutics.

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Correspondence to Priyadarshini P. Pai or Sukanta Mondal .

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Pai, P.P., Mondal, S. (2017). Intriguing Cystine-Knot Miniproteins in Drug Design and Therapeutics. In: Cruz, L., Luo, S. (eds) Toxins and Drug Discovery. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6452-1_25

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