An Efficient Approach for the Total Synthesis of Cyclotides by Microwave Assisted Fmoc-SPPS

Park, Sungkyu; Gunasekera, Sunithi; Aboye, Teshome Leta; Göransson, Ulf

doi:10.1007/s10989-010-9221-0

Cited by 22 publications

(32 citation statements)

References 54 publications

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“…a TGT resin) allowing for the intact side-chain protection after cleavage from the support. 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].…”

Section: Backbone Macrocyclizationmentioning

confidence: 99%

“…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%

“…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. 3) [173]. Installation of a thioester as on-resin cleavable linker seems more elegant, as no special modification is required [171].…”

Section: Backbone Macrocyclizationmentioning

confidence: 99%

“…Following incorporation of a carboxyterminal thioester, NCL leads to efficient formation of cyclic peptides [171,173]. Although to date its mechanism is not fully understood, it is commonly accepted that a cascade of intramolecular thioesterifications between the internal thiols and the carboxyterminus takes place [167].…”

Section: Backbone Macrocyclizationmentioning

confidence: 99%

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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%

Section: Backbone Macrocyclizationmentioning

confidence: 99%

Section: Backbone Macrocyclizationmentioning

confidence: 99%

Section: Backbone Macrocyclizationmentioning

confidence: 99%

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Synthetic Cystine-Knot Miniproteins – Valuable Scaffolds for Polypeptide Engineering

Avrutina

2016

Advances in Experimental Medicine and Biology

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“…[14] This synthetic limitation enhances the requirement for alternative recombinant-based strategies for cyclotide production.…”

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confidence: 99%

Making Ends Meet: Chemically Mediated Circularization of Recombinant Proteins

Cowper¹,

Craik²,

Macmillan³

2013

ChemBioChem

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Amide‐Forming Ligation Reactions

2019

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One of the long‐standing pursuits of synthetic organic chemists is the development of chemical methods for the synthesis of peptides and proteins as tools for understanding biological processes and providing therapeutic solutions to human diseases. The advent of chemoselective ligation reactions for the chemical synthesis of peptides and proteins has enabled synthetic chemists to realize this long‐held dream. In an amide‐forming ligation reaction, two uniquely placed functional groups within the peptide allow peptide or protein segments to be joined in a chemoselective manner with an amide bond. In this chapter, some of the early methods based on principles of the capture/rearrangement strategy for ligation of peptides are catalogued, followed by some of the most versatile and well‐established contemporary methods for the preparation of linear/cyclic peptides and proteins such as the native chemical ligation (NCL) and the α‐ketoacid–hydroxylamine (KAHA) ligation. The chapter concludes with some of the most promising new generation ligation methods such as the potassium acyltrifluoroborate–hydroxylamine (KAT) ligation. The tremendous progress in the past two decades in the development of several ligation methods that rely on a pair of unique functional groups is set to expand the horizons of fully functional proteins and multi‐protein assemblies that are purely synthetically prepared. Although contemporary ligation reactions do not match the speed and efficiency at which proteins are assembled in biological systems, the repertoire of chemoselective amide‐forming ligation methods has already enabled synthetic protein chemistry to surpass biology in terms of chemical and structural diversity.

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An Efficient Approach for the Total Synthesis of Cyclotides by Microwave Assisted Fmoc-SPPS

Cited by 22 publications

References 54 publications

Synthetic Cystine-Knot Miniproteins – Valuable Scaffolds for Polypeptide Engineering

Synthetic Cystine-Knot Miniproteins – Valuable Scaffolds for Polypeptide Engineering

Making Ends Meet: Chemically Mediated Circularization of Recombinant Proteins

Amide‐Forming Ligation Reactions

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