title: Chemical synthesis, backbone cyclization and oxidative folding of cystine-knot peptides: promising scaffolds for applications in drug design.
abstract: Cystine-knot peptides display exceptional structural, thermal, and biological stability. Their eponymous motif consists of six cysteine residues that form three disulfide bonds, resulting in a notably rigid structural core. Since they highly tolerate either rational or combinatorial changes in their primary structure, cystine knots are considered to be promising frameworks for the development of peptide-based pharmaceuticals. Despite their relatively small size (two to three dozens amino acid residues), the chemical synthesis route is challenging since it involves critical steps such as head-to-tail cyclization and oxidative folding towards the respective bioactive isomer. Herein we describe the topology of cystine-knot peptides, their synthetic availability and briefly discuss potential applications of engineered variants in diagnostics and therapy.
authors.affiliation: Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Reinwarth
authors.forename: Daichi
authors.initials: D
authors.lastname: Nasu
authors.forename: Harald
authors.initials: H
authors.lastname: Kolmar
authors.forename: Olga
authors.initials: O
authors.lastname: Avrutina
mesh_terms: D000595:Amino Acid Sequence; D003500:Cyclization; D047168:Cystine Knot Motifs; D057771:Cystine-Knot Miniproteins / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017510:Protein Folding; D055550:Protein Stability
chemical_list: D057771:Cystine-Knot Miniproteins