Knottins display a variety of biological functions


  • ‣ Some knottins are thought to perform their action via interaction with a receptor.
  • ‣ This has led several authors to use the slightly restrictive name "Inhibitor Cystine Knot" (ICK)
  • ‣ Different activities are located on different parts of the molecules, and almost all Knottin loops have been implied in one ore more function.
  • ‣ The major known biological functions exerted by Knottins are briefly outlined below.
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Analgesics

Anthelmintic

Anti-ED

Antimalarial

Antimicrobials

Antitumors

Protease inhibitors

Toxins

Insecticids

Others

Others

Besides above activities, it is worth noting that

  • Knottin-1 gene of whitefly [ Hariton Shalev et al., 2016] displays antiviral activity on tomato yellow leaf curl virus.

  • Circulin A, cycloviolins A-D and kalata B8 [ Hallock et al., 2000; Daly et al., 2006] displays anti-HIV activity.

  • Cyclopsychotride A inhibits neurotensin binding to HT-29 cell membranes.
  • Cycloviolacin H4 displays the highest hemolytic activity among cyclotides. It has been proposed that this activity correlates with the size of a surface-exposed hydrophobic patch [ Chen et al., 2006].

  • Kalata B1 is used in traditional medicine for its uterotonic activity
  • Agouti and Agouti-related proteins (AgRP) are endogeneous antagonists of the melanocortin receptors (MCRs) [Gantz and Fung, 2003; Stutz et al., 2005; Pritchard et al., 2005]. The normal role of agouti in mammals is to determine coat color in conjunction with MC1R and the melanocortin peptide α-melanocyte-stimulating hormone (α-MSH). Hence the term agouti that refers to a hair color pattern characterized by subapical yellow bands. Interestingly, agouti also acts as an antagonist of hypothalamic α-MSH, a major satiety factor, and is thus involved in obesity.
    Studies in humans revealed associations of AGRP single nucleotide polymorphisms with resistance to obesity. Administration or overexpression of AgRP increases intake of fat diet On the other hand, absence or reduced functionality of AgRP leads to an increased lifespan [Ilnytska & G. Argyropoulos, 2008; Tracy et al., 2008]. As the melanocortin system is involved in diverse physiological functions, including pigmentation, energy homeostasis, inflammation, fat intake and sexual function. Melanocortin-based drugs are therefore considered for the treatment of skin cancer, obesity, erectile dysfunction, inflammatory diseases, pain, etc.