Urethane protected amino acid N-carboxyanhydrides and their use in peptide synthesis

Fuller, Wayne A.; Cohen, Michael P.; Shabankareh, Mitra; Blair, Robert K.; Goodman, Murray; Naider, Fred

doi:10.1021/ja00176a063

Cited by 118 publications

(54 citation statements)

References 9 publications

(2 reference statements)

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“…H-Pro-Lys-Met-CysGly-Val-NH,, H-Pro-Lys-Met-Ser-Gly-Val-NH, and H-Lys-Pro-ArgCys-Gly-Val-NH,, were synthesized in high-pressure continuous-flow reactors according to the Fmoc/tBu strategy [I I] using the modified Rink-linker on Tentagel S RAM resin (Rapp, Tubingen). Fmoc-Gly, Fmoc-Ser(tBu), Fmoc-Leu and Fmoc-Lys(Boc) were coupled as NCA derivatives [12], and Fmoc-Pro-OH, Fmoc-Val-OH, Fmoc-Cys(StBu)-OH and Fmoc-Arg(Pmc)-OH via TBTUIHOBtlDIEA (1: 1:2). Intermediate Fmoc removal and final acidolytic cleavage steps were performed as described previously 1131.…”

Section: Methodsmentioning

confidence: 99%

“…1. Sequence alignment and secondary structure prediction according to Chou and Fasman [11,12] present. The cysteine residue closest to the N-terminus of the mature protein is located in the PKMCGVT homologous sequence portion and therefore 21 (H&e), 23 (Jararhagin, Trigramin) or 24 (Rhodostamin) residues apart from the presumed starting residue of the mature protein sequence.…”

Section: Aiignments Of Precursor Sequencesmentioning

confidence: 99%

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Activation of snake venom metalloproteinases by a cysteine switch‐like mechanism

et al. 1993

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The cDNAs of several snake venom zinc endopeptidases code for a putative propeptide, which includes the conserved cysteine-containing sequence PKMCGVT. It has been suggested that binding of the cysteine thiol function to the active-site zinc, resulting in inactivation of the catalytic domain, occurs in a mode similar to the 'cysteine switch' mechanism proposed for matrix metalloproteinases. In order to confirm this hypothesis, inhibition kinetics have been performed on the metalloproteinase adamalysin II of the venom of the snake Crotalus adumanteus using several cysteine peptides. Among these the synthetic hexapeptide PKMCGV-NH*, corresponding to the conserved sequence portion of the known propeptides, was found to be by far the strongest inhibitor of this proteinase with a K, of 3.4,uM. The inhibitory potencies of an equivalent peptide with the L-Cys replaced by a D-Cys or by an t_-Ser as well as of reduced glutathione, cysteine and two unrelated cysteine peptides were by one to two orders of magnitudes lower. These findings strongly support a cysteine switch-Iike mechanism even for activation of the snake venom metalloproteinases.Cysteine switch; Matrix metalloproteinase; Snake venom metalloproteina~; Adamalysin; Proteinase activation; Stability of cysteine peptide

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Section: Methodsmentioning

confidence: 99%

Section: Aiignments Of Precursor Sequencesmentioning

confidence: 99%

Activation of snake venom metalloproteinases by a cysteine switch‐like mechanism

et al. 1993

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“…4-Nitrophenylsulfenylchlorid (Nps-Cl) und 2,4-Dinitrophenylsulfenylchlorid erwiesen sich jedoch als so reaktiv, dass mithilfe von Triethylamin eine quantitative Substitution möglich war. Ferner kristallisieren die meisten Nps-NCAs gut, sodass mehrere Arbeitsgruppen [55][56][57][58][59] [60][61][62] markierte daher einen beträchtlichen Fortschritt. Der entscheidende Trick für die erfolgreiche N-Acylierung von NCAs ohne Polymerisation war die Verwendung von N-Methylmorpholin als Base.…”

Section: Introductionunclassified

“…Aufgrund der besonderen Anwendungsmöglichkeiten von Boc-NCAs avancierten diese Verbindungen zu Handelsprodukten. Boc-NCAs erwiesen sich als besonders nützlich bei der Festphasen-Peptidsynthese, [60] weil in ihrer Struktur hohe Reaktivität mit relativ geringer sterischer Hinderung kombiniert ist. Ein genereller Nachteil sowohl von Nps-NCAs als auch von UNCAs ist jedoch deren hohe Anfälligkeit für Racemisierungen.…”

Section: Introductionunclassified

Polypeptide und 100 Jahre Chemie der α‐Aminosäure‐N‐carboxyanhydride

Kricheldorf

2006

Angewandte Chemie

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Synthese und Polymerisation von α‐Aminosäure‐N‐carboxyanhydriden (NCAs) wurden erstmals im Jahre 1906 von Herrmann Leuchs beschrieben. Seit dieser Zeit wurden diese cyclischen, sehr reaktiven α‐Aminosäurederivate mehrfach zur schrittweisen Peptidsynthese eingesetzt, sie wurden aber vor allem zur Herstellung von Polypeptiden durch ringöffnende Polymerisation (ROP) verwendet. Es werden nun neue Aspekte der ringöffnenden Polymerisation diskutiert, z. B. die Verwendung neuartiger metallorganischer Initiatoren oder die Entstehung cyclischer Polypeptide. Des Weiteren werden Architekturen wie Diblock‐, Triblock‐ und Multiblockcopolymere sowie sternförmige oder hochverzweigte Polypeptide vorgestellt. Ferner werden lyotrope und thermotrope Polypeptide sowie die Verwendung von Polypeptiden als Pharmaka oder Pharmakaträger besprochen. Schließlich wird die Rolle von NCAs im Konzept der molekularen Evolution diskutiert.

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“…N-Carboxy-α-aminoacid anhydrides may be N-alkoxycarbonylated in the presence of base to give urethane protected derivatives (UNCA) (Scheme 29). 34 Fmoc derivatives are crystalline, with good shelf-life properties, that react rapidly with amines to give Fmoc acyl derivatives and carbon dioxide as the only products. Over-reaction cannot occur because deprotection is needed before another residue can be added.…”

Section: Scheme 28mentioning

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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Urethane protected amino acid N-carboxyanhydrides and their use in peptide synthesis

Cited by 118 publications

References 9 publications

Activation of snake venom metalloproteinases by a cysteine switch‐like mechanism

Activation of snake venom metalloproteinases by a cysteine switch‐like mechanism

Polypeptide und 100 Jahre Chemie der α‐Aminosäure‐N‐carboxyanhydride

Evolution of amide bond formation

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