In Planta Discovery and Chemical Synthesis of Bracelet Cystine Knot Peptides from Rinorea bengalensis

Cyclotides are a group of plant-derived peptides with a head-to-tail cyclized backbone that is stabilized by three knotted disulfide bonds. Their exceptional stability and tolerance for residue substitutions have led to interest in their application as drug design scaffolds. To date, chemical synthesis has been the dominant methodology for producing cyclotides and their analogues. Native chemical ligation is the most common strategy to generate the cyclic backbone and has been highly successful at producing a wide range of cyclotides for studies of structure–activity relationships. Both this and other chemical approaches require a specific linker at the C-terminus and typically involve a non-directed folding (disulfide oxidation) regimen, which can sometimes be a limiting factor in final yields. Following the recent discovery of enzymes involved in peptide cyclization in planta, site-specific and highly efficient enzymatic ligations have been used for synthetic cyclotide backbone cyclization. In this review, chemical synthesis strategies and approaches involving cyclization via enzymes for the production of cyclotides are described.

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Chemical Synthesis, Backbone Cyclization and Oxidative Folding of Cystine-knot Peptides — Promising Scaffolds for Applications in Drug Design

Molecules ◽

10.3390/molecules171112533 ◽

2012 ◽

Vol 17 (11) ◽

pp. 12533-12552 ◽

Cited By ~ 26

Author(s):

Michael Reinwarth ◽

Daichi Nasu ◽

Harald Kolmar ◽

Olga Avrutina

Keyword(s):

Drug Design ◽

Chemical Synthesis ◽

Oxidative Folding ◽

Cystine Knot ◽

Backbone Cyclization

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Chemical Synthesis and Folding Pathways of Large Cyclic Polypeptides: Studies of the Cystine Knot Polypeptide Kalata B1†

Biochemistry ◽

10.1021/bi990605b ◽

1999 ◽

Vol 38 (32) ◽

pp. 10606-10614 ◽

Cited By ~ 169

Author(s):

Norelle L. Daly ◽

Steve Love ◽

Paul F. Alewood ◽

David J. Craik

Keyword(s):

Chemical Synthesis ◽

Kalata B1 ◽

Cystine Knot ◽

Folding Pathways

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Sinapic Acid and Sinapate Esters in Brassica: Innate Accumulation, Biosynthesis, Accessibility via Chemical Synthesis or Recovery From Biomass, and Biological Activities

Frontiers in Chemistry ◽

10.3389/fchem.2021.664602 ◽

2021 ◽

Vol 9 ◽

Author(s):

V. P. Thinh Nguyen ◽

Jon D. Stewart ◽

Irina Ioannou ◽

Florent Allais

Keyword(s):

Chemical Synthesis ◽

Biological Activities ◽

Sinapic Acid ◽

Industrial Wastes ◽

Biological Processes ◽

In Planta ◽

Food Industries ◽

Plant Parts ◽

Anti Cancer ◽

The Family

Sinapic acid (SinA) and corresponding esters are secondary metabolites abundantly found in plants of Brassica family. Belonging to the family of p-hydroxycinnamic acids, SinA and its esters analogues are present in different plant parts and involved in multiple biological processes in planta. Moreover, these metabolites are also found in relatively large quantities in agro-industrial wastes. Nowadays, these metabolites are increasingly drawing attention due to their bioactivities which include antioxidant, anti-microbial, anti-cancer and UV filtering activities. As a result, these metabolites find applications in pharmaceutical, cosmetic and food industries. In this context, this article reviews innate occurrence, biosynthesis, accessibility via chemical synthesis or direct extraction from agro-industrial wastes. Biological activities of SinA and its main corresponding esters will also be discussed.

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