Synthesis of Proteins by Native Chemical Ligation Using Fmoc‐Based Chemistry

Camarero, Julio A.; Mitchell, Alexander R.

doi:10.1002/chin.200633263

Cited by 2 publications

(2 citation statements)

References 65 publications

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“…To the resulting peptide the thiol is coupled yielding the desired thioester [173]. This methodology, being generally compatible with the common Fmoc-strategy, is complicated by the unpredictable solubility of fully protected peptides of that size and undesired carboxyterminal racemization [173,174]. Therefore a glycine as aminoterminal and a cysteine as carboxyterminal residue at the site of macrocyclization are often chosen, as glycine is the only non-chiral amino acid and glycine-cysteine combinations exist in a number of cystine-knot peptides (Fig.…”

Section: Backbone Macrocyclizationmentioning

confidence: 99%

Synthetic Cystine-Knot Miniproteins – Valuable Scaffolds for Polypeptide Engineering

Avrutina

2016

Advances in Experimental Medicine and Biology

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Peptides with the cystine-knot architecture, often termed knottins, are promising scaffolds for biomolecular engineering. These unique molecules combine diverse bioactivities with excellent structural, thermal, and proteolytical stability. Being different in the composition and structure of their amino acid backbone, knottins share the same core element, namely cystine knot, which is built by six cysteine residues forming three disulfides upon oxidative folding. This motif ensures a notably rigid framework that highly tolerates both rational and combinatorial changes in the primary structure. Being accessible through recombinant production and total chemical synthesis, cystine-knot miniproteins can be endowed with novel bioactivities by variation of surface-exposed loops and incorporation of non-natural elements within their non-conserved regions towards the generation of tailor-made peptidic compounds. In this chapter the topology of cystine-knot peptides, their synthesis and applications for diagnostics and therapy is discussed.

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Section: Backbone Macrocyclizationmentioning

confidence: 99%

Synthetic Cystine-Knot Miniproteins – Valuable Scaffolds for Polypeptide Engineering

Avrutina

2016

Advances in Experimental Medicine and Biology

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“…Chemical synthesis using a solid-phase approach has been utilized to generate native cyclotide structures as well as grafted analogues [52][53][54][55][56]. This method uses an intramolecular native chemical ligation [57], in which the peptide sequence contains an N-terminal cysteine and an α-thioester group at the C-terminus [58][59][60]. Both tert-butyloxyxarbonyl (Boc)-and 9-fluorenyloxycarbonyl (Fmoc)-based chemistries have been used to incorporate C-terminal thioesters during chain assembly (Boc) [61][62][63] or using a safety-catch based linkers (Fmoc) [60,[64][65][66][67].…”

Section: Chemical Synthesis Of Cyclotidesmentioning

confidence: 99%

Biological Activities of Natural and Engineered Cyclotides, a Novel Molecular Scaffold for Peptide-Based Therapeutics

Garcia¹,

Camarero²

2010

CMP

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Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (≈30 amino acids long) that share a disulfide-stabilized core characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently more than 100 sequences of different cyclotides have been characterized and the number is expected to increase dramatically in the coming years. Considering their stability, biological activities and ability to cross the cell membrane, cyclotides can be exploited to develop new peptide-based drugs with high potential for success. The cyclotide scaffold can be engineered or evolved using molecular evolution to inhibit proteinprotein interactions implicated in cancer and other human diseases, or design new antimicrobial. The present review reports the biological diversity and therapeutic potential of natural and engineered cyclotides.

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Synthesis of Proteins by Native Chemical Ligation Using Fmoc‐Based Chemistry

Cited by 2 publications

References 65 publications

Synthetic Cystine-Knot Miniproteins – Valuable Scaffolds for Polypeptide Engineering

Synthetic Cystine-Knot Miniproteins – Valuable Scaffolds for Polypeptide Engineering

Biological Activities of Natural and Engineered Cyclotides, a Novel Molecular Scaffold for Peptide-Based Therapeutics

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