Peptide Segment Coupling by Prior Ligation and Proximity-Induced Intramolecular Acyl Transfer

Coltart, Don M.

doi:10.1016/s0040-4020(00)00147-2

Cited by 87 publications

(69 citation statements)

References 82 publications

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“…1,2,17 Native chemical ligation (NCL) for the synthesis of peptides and proteins, and its enzyme-promoted biochemical equivalent, expressed protein ligation, [18][19][20][21] is one such reaction that takes advantage of the sulfhydryl group and which uses it to great advantage in the highly chemoselective formation of amide bonds in aqueous solution. 10,[21][22][23][24][25][26][27][28][29][30][31] Another thiol-based method, the selective formation of mixed disulfides, is both one of the oldest and most enduring of ligation methods.…”

Section: Introductionmentioning

confidence: 99%

Dechalcogenative Allylic Selenosulfide and Disulfide Rearrangements: Complementary Methods for the Formation of Allylic Sulfides in the Absence of Electrophiles. Scope, Limitations, and Application to the Functionalization of Unprotected Peptides in Aqueous Media.

et al. 2007

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Primary allylic selenosulfates (seleno Bunte salts) and selenocyanates transfer the allylic selenide moiety to thiols giving primary allylic selenosulfides, which undergo rearrangement in the presence of PPh 3 with the loss of selenium to give allylically rearranged allyl alkyl sulfides. This rearrangement may be conducted with prenyl-type selenosulfides to give isoprenyl alkyl sulfides. Alkyl secondary and tertiary allylic disulfides, formed by sulfide transfer from allylic heteroaryl disulfides to thiols, undergo desulfurative allylic rearrangement on treatment with PPh 3 in methanolic acetonitrile at room temperature. With nerolidyl alkyl disulfides this rearrangement provides an electrophile-free method for the introduction of the farnesyl chain onto thiols. Both rearrangements are compatible with the full range of functionality found in the proteinogenic amino acids and it is demonstrated that the desulfurative rearrangement functions in aqueous media, enabling the derivatization of unprotected peptides. It is also demonstrated that the allylic disulfide rearrangement can be inducted in the absence of phosphine at room temperature by treatment with piperidine, or simply by refluxing in methanol. Under these latter conditions the reaction is also applicable to allyl aryl disulfides, providing allylically rearranged allyl aryl sulfides in good yields.

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Section: Introductionmentioning

confidence: 99%

Dechalcogenative Allylic Selenosulfide and Disulfide Rearrangements: Complementary Methods for the Formation of Allylic Sulfides in the Absence of Electrophiles. Scope, Limitations, and Application to the Functionalization of Unprotected Peptides in Aqueous Media.

et al. 2007

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“…[83][84][85][86] While a review of the field is beyond the scope of this report, the importance of the process merits a brief discussion of the chemistry involved. NCL is one of the few nonenzymatic reactions that can join two unprotected peptide segments to generate a ligated peptide/protein product with a native peptide bond at the reaction site.…”

Section: Native Chemical Ligation (Ncl) Approachesmentioning

confidence: 99%

“…84 The process has been applied to the total chemical synthesis of enzymes. A sortase-mediated ligation of proteins to both peptides and non-peptides was demonstrated in vitro to be a new method for protein engineering.…”

Section: Scheme 51mentioning

confidence: 99%

Evolution of amide bond formation

Joullié¹,

Lassen²

2010

Arkivoc

160

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This paper is dedicated to Drs Bruce E. Maryanoff and Cynthia A. Maryanoff for their outstanding contribution to organic chemistry as industrial chemists AbstractThe presence of carboxamide groups is found in a large array of biologically important compounds. Peptides and proteins play an important role in modern biology. A key step in peptide production is the formation of the peptide bond, which involves amide bond formation. Chemical synthesis of large peptides by intermolecular coupling of smaller peptides using conventional peptide bond-forming techniques did not realize its potential advantages until recently. Using an approach based on highly specific and efficient chemical ligation of two peptide segments, the two subunits were ligated to form a new peptide bond. Native chemical ligation extended the concept by creating a native peptide bond and providing new approaches to protein engineering.

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“…So far, acyl transfer reactions have been the subject of extensive mechanistic studies [16], and their role in protein biosynthesis and splicing [17], peptide synthesis and solubilization [18], prodrug design [19] and native chemoselective ligation strategies [20] has attracted much attention. Our focus over the last few years was directed toward the elaboration of the concept of 'switch-peptides' for the study of peptide self-assembly, secondary structure formation and disruption [15] [21].…”

Section: The Concept Of Switch-peptidesmentioning

confidence: 99%

Switch-Peptides: From Conformational Studies to Alzheimer's Disease

Saucède¹,

Santos²,

Chandravarkar³

et al. 2006

Chimia

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Studies on designed peptides that exhibit high tendencies for medium-induced conformational transitions have recently attracted much attention because structural changes are considered as molecular key processes in degenerative diseases. The experimental access to these events has been limited so far mainly due to the intrinsic tendency of the involved polypeptides for self-association and aggregation, e.g. amyloid β plaque formation, thought to be at the origin of Alzheimer's disease. We have developed a new concept termed 'switchpeptides' which allows the controlled onset of polypeptide folding and misfolding in vitro and in vivo, starting from a soluble, non-toxic precursor molecule. As a major feature, the folding process is initiated by enzyme-triggered N,O-acyl migrations restoring the native peptide backbone in situ. As the folding is set off in the moment of creating the bioactive molecule ('in statu nascendi', ISN), our concept allows for the first time the investigation of the early steps of protein misfolding as relevant in degenerative diseases, opening new perspectives for the rational design of therapeutically relevant compounds.

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Peptide Segment Coupling by Prior Ligation and Proximity-Induced Intramolecular Acyl Transfer

Cited by 87 publications

References 82 publications

Dechalcogenative Allylic Selenosulfide and Disulfide Rearrangements: Complementary Methods for the Formation of Allylic Sulfides in the Absence of Electrophiles. Scope, Limitations, and Application to the Functionalization of Unprotected Peptides in Aqueous Media.

Dechalcogenative Allylic Selenosulfide and Disulfide Rearrangements: Complementary Methods for the Formation of Allylic Sulfides in the Absence of Electrophiles. Scope, Limitations, and Application to the Functionalization of Unprotected Peptides in Aqueous Media.

Evolution of amide bond formation

Switch-Peptides: From Conformational Studies to Alzheimer's Disease

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