Natural Functions and Structure–Activity Relationships of Cyclotides

Oguis, Georgianna Kae; Kan, Meng‐Wei; Craik, David J.

doi:10.1016/bs.abr.2015.10.001

Cited by 6 publications

(5 citation statements)

References 95 publications

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“…This ability to lyse red blood cells occurs via its interaction with membranes—the same mechanism by which it kills microbes. So far, it has been observed that the level of hemolytic activity varies from peptide to peptide and often correlates with parasiticidal activity [ 127 ]. Cycloviolacin H4, Cycloviolacin Y5, VarvE, characterized from Viola hederacea , Viola yedoensis , and Viola tricolor are examples of peptides which have shown hemolytic activity [ 128 ].…”

Section: Limitations To the Pharmaceutical Applications Of Knottin-ri...mentioning

confidence: 99%

Nutritional and Pharmaceutical Applications of Under-Explored Knottin Peptide-Rich Phytomedicines

Attah

Lawal

Yusuf

et al. 2022

Plants

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Phytomedicines reportedly rich in cystine knot peptides (Knottins) are found in several global diets, food/herbal supplements and functional foods. However, their knottin peptide content has largely been unexplored, notably for their emerging dual potentials at both the food and medicine space. The nutritional roles, biological targets and mechanism(s) of activity of these knotted peptides are largely unknown. Meanwhile, knottins have recently been unveiled as emerging peptide therapeutics and nutraceuticals of primary choice due to their broad spectrum of bioactivity, hyper stability, selective toxicity, impressive selectivity for biomolecular targets, and their bioengineering applications. In addition to their potential dietary benefits, some knottins have displayed desirable limited toxicity to human erythrocytes. In an effort to appraise what has been accomplished, unveil knowledge gaps and explore the future prospects of knottins, an elaborate review of the nutritional and pharmaceutical application of phytomedicines rich in knottins was carried out. Herein, we provide comprehensive data on common dietary and therapeutic knottins, the majority of which are poorly investigated in many food-grade phytomedicines used in different cultures and localities. Findings from this review should stimulate scientific interest to unveil novel dietary knottins and knottin-rich nutraceutical peptide drug candidates/leads with potential for future clinical application.

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Section: Limitations To the Pharmaceutical Applications Of Knottin-ri...mentioning

confidence: 99%

Nutritional and Pharmaceutical Applications of Under-Explored Knottin Peptide-Rich Phytomedicines

Attah

Lawal

Yusuf

et al. 2022

Plants

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“…Several linear and cyclic cystine-knot peptides also displayed toxicity against a range of cell lines derived from different cancer types [4,43]. However, the cytotoxic activity against cancer cells is not specific, as some cystine-knot peptides can also target healthy cells [43,44]. Various cyclotides from both the bracelet and Möbius subfamilies displayed anti-HIV activity [22,27,28] and uterotonic activity [45].…”

Section: Biological Activities and Molecular Targets Of Cystine-knot mentioning

confidence: 99%

“…Many cystine‐knot peptides have antimicrobial properties showing inhibitory effects on microbial cell growth. Several linear and cyclic cystine‐knot peptides also displayed toxicity against a range of cell lines derived from different cancer types . However, the cytotoxic activity against cancer cells is not specific, as some cystine‐knot peptides can also target healthy cells .…”

Section: Biological Activities and Molecular Targets Of Cystine‐knot mentioning

confidence: 99%

Plant cystine‐knot peptides: pharmacological perspectives

Molesini

Treggiari

Dalbeni

et al. 2016

Brit J Clinical Pharma

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Cystine-knot miniproteins are a class of 30-50 amino acid long peptides widespread in eukaryotic organisms. Due to their very peculiar three-dimensional structure, they exhibit high resistance to heat and peptidase attack. The cystine-knot peptides are well represented in several plant species including medicinal herbs and crops. The pharmacological interest in plant cystine-knot peptides derives from their broad biological activities, mainly cytotoxic, antimicrobial and peptidase inhibitory and in the possibility to engineer them to incorporate pharmacophoric information for oral delivery or disease biomonitoring. The mechanisms of action of plant cystine-knot peptides are still largely unknown, although the capacity to interfere with plasma membranes seems a feature common to several cystine-knot peptides. In some cases, such as potato carboxypetidase inhibitor (PCI) and tomato cystine-knot miniproteins (TCMPs), the cystine-knot peptides target human growth factor receptors either by acting as growth factor antagonist or by altering their signal transduction pathway. The possibility to identify specific molecular targets of plant cystine-knot peptides in human cells opens novel possibilities for the pharmacological use of these peptides besides their use as scaffold to develop stable disease molecular markers and therapeutic agents.

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“…21 Indigenous medicinal uses of plants have also helped in some of these discoveries, such as the use of kalata B1 as a uterotonic agent in Africa, as described earlier. 53 and so here we focus on just one recently reported bio-activity, namely immunomodulation. To place this work in context we note that cyclosporin A, a non-ribosomal cyclic depsipeptide is a clinically used immunosuppressive drug.…”

Section: Introductionmentioning

confidence: 99%

Ribosomally-synthesised cyclic peptides from plants as drug leads and pharmaceutical scaffolds

Craik

Rehm

Tombling

et al. 2018

Bioorganic & Medicinal Chemistry

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Owing to their exceptional stability and favourable pharmacokinetic properties, plant-derived cyclic peptides have recently attracted significant attention in the field of peptide-based drug design. This article describes the three major classes of ribosomally-synthesised plant peptides - the cyclotides, the PawS-derived peptides and the orbitides - and reviews their applications as leads or scaffolds in drug design. These ribosomally-produced peptides have a range of biological activities, including anti-HIV, cytotoxic and immunomodulatory activity. In addition, recent interest has focused on their use as scaffolds to stabilise bioactive peptide sequences, thereby enhancing their biopharmaceutical properties. There are now more than 30 published papers on such 'grafting' applications, most of which have been reported only in the last few years, and several such studies have reported in vivo activity of orally delivered cyclic peptides. In this article, we describe approaches to the synthesis of cyclic peptides and their pharmaceutically-grafted derivatives as well as outlining their biosynthetic routes. Finally, we describe possible bioproduction routes for pharmaceutically active cyclic peptides, involving plants and plant suspension cultures.

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Natural Functions and Structure–Activity Relationships of Cyclotides

Cited by 6 publications

References 95 publications

Nutritional and Pharmaceutical Applications of Under-Explored Knottin Peptide-Rich Phytomedicines

Nutritional and Pharmaceutical Applications of Under-Explored Knottin Peptide-Rich Phytomedicines

Plant cystine‐knot peptides: pharmacological perspectives

Ribosomally-synthesised cyclic peptides from plants as drug leads and pharmaceutical scaffolds

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