Chemie und Biologie von Theta‐Defensinen

Conibear, Anne C.; Craik, David J.

doi:10.1002/ange.201402167

Cited by 13 publications

(1 citation statement)

References 120 publications

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“…The cysteine‐rich peptides exhibited antimicrobial activity against Gram‐positive, Gram‐negative bacteria, fungi, and retroviruses. In 2014, Conibear and Craik reviewed the peptides and their applications extensively [27] . Here, we precisely focused on the two θ‐defensins used as scaffolds for molecular grafting; heterodimer RTD‐1 and homodimer BTD‐2.…”

Section: Theta Defensinsmentioning

confidence: 99%

Cysteine‐Rich Peptides: Hyperstable Scaffolds for Protein Engineering

2020

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Cysteine‐rich peptides (CRPs) are small proteins of less than 100 amino acids in length characterized by the presence of disulfide bridges and common end‐to‐end macrocyclization. These properties confer hyperstability against high temperatures, salt concentration, serum presence, and protease degradation to CRPs. Moreover, their intercysteine domains (loops) are susceptible to residue hypervariability. CRPs have been successfully applied as stable scaffolds for molecular grafting, a protein engineering process in which cysteine‐rich structures provide higher thermodynamic and metabolic stability to an epitope and acquire new biological function(s). This review describes the successes and limitations of seven cysteine‐rich scaffolds, their bioactive epitopes, and the resulting grafted peptides.

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Section: Theta Defensinsmentioning

confidence: 99%

Cysteine‐Rich Peptides: Hyperstable Scaffolds for Protein Engineering

2020

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Generation of a Genetically Encoded, Photoactivatable Intein for the Controlled Production of Cyclic Peptides

et al. 2014

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Cyclic peptides are important natural products and hold great promise for the identification of new bioactive molecules. The split-intein-mediated SICLOPPS technology provides a generic access to fully genetically encoded head-totail cyclized peptides and large libraries thereof (SICLOPPS = split-intein circular ligation of peptides and proteins). However, owing to the spontaneous protein splicing reaction, product formation occurs inside cells, making peptide isolation inconvenient and precluding traditional in vitro assays for inhibitor discovery. The design of a genetically encoded, lightdependent intein using the photocaged tyrosine derivative ortho-nitrobenzyltyrosine incorporated at an internal, noncatalytic position is now reported. Stable intein precursors were purified from the E. coli expression host and subsequently subjected to light activation in vitro for both the regular protein splicing format and cyclic peptide production, including the natural product segetalin H as an example. The activity of the intein could also be triggered in living cells.

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Precisely Regulated and Efficient Locking of Linear Peptides into Stable Multicyclic Topologies through a One‐Pot Reaction

et al. 2017

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We report the discovery of a small phenyl molecule with four isosteric thiolate‐reactive groups of sequentially varied reactivity. This molecule was exploited in combination with cysteine/penicillamine thiolates of different nucleophilic reactivity for precisely regulated and efficient locking (PROP‐locking) of linear peptides into multicyclic topologies through a one‐pot reaction. The PROP‐locking relies on multistep and sequential thiolate/fluorine nucleophilic substitutions, which is not only rapid but highly specific, thus enabling rapid locking of peptides with high amino acid diversities without protecting groups. Several tricyclic peptide templates and bioactive peptides were designed and synthesized using the PROP‐locking strategy. We believe that tricyclic peptides precisely locked through stable thioether bonds should be promising structurally constrained scaffolds for developing potential therapeutics and target ligands.

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Chemie und Biologie von Theta‐Defensinen

Cited by 13 publications

References 120 publications

Cysteine‐Rich Peptides: Hyperstable Scaffolds for Protein Engineering

Cysteine‐Rich Peptides: Hyperstable Scaffolds for Protein Engineering

Generation of a Genetically Encoded, Photoactivatable Intein for the Controlled Production of Cyclic Peptides

Precisely Regulated and Efficient Locking of Linear Peptides into Stable Multicyclic Topologies through a One‐Pot Reaction

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