The reaction between thiols and 8-azidoadenosine derivatives

Cartwright, Iain L.; Hutchinson, D. W.; Armstrong, Victor W.

doi:10.1093/nar/3.9.2331

Cited by 107 publications

(66 citation statements)

References 8 publications

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“…Anders als Aldehyde und Ketone kommen Azide in biologischen Systemen nicht vor [137] und weisen zugleich eine orthogonale Reaktivität zur Mehrzahl der biologischen funktionellen Gruppen auf. Die Azidfunktion ist klein [138][139][140] und wirkt daher nur minimal störend [143][144][145] Die Reduktion von Alkylaziden verläuft bei physiologischem pH-Wert relativ langsam, es gibt allerdings Hinweise, dass cytosolisches Glutathion das Azid in 3'-Azidothymidin reduzieren kann. [146] Wir befassten uns mit diesem Problem im Zusammenhang mit der Markierung von Glycanen mit Azidozuckern.…”

Section: Staudinger-ligation Von Aziden Mit Triarylphosphanenunclassified

Bioorthogonale Chemie – oder: in einem Meer aus Funktionalität nach Selektivität fischen

2009

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Biomoleküle in ihrer natürlichen Umgebung zu erforschen, ist wegen der enormen Komplexität zellulärer Systeme eine anspruchsvolle Aufgabe. In den letzten Jahren entwickelte Methoden zur selektiven Modifizierung biologischer Spezies in lebenden Systemen haben neue Einblicke in zelluläre Prozesse gegeben. Grundlage dieser neuen Techniken sind bioorthogonale chemische Reaktionen, deren Komponenten unter physiologischen Bedingungen in Gegenwart zahlreicher Funktionalitäten, wie sie zur Erhaltung des Lebens notwendig sind, schnell und selektiv miteinander reagieren müssen. Hier beschreiben wir die bisher entwickelten bioorthogonalen chemischen Reaktionen und wie sie zum Studium von Biomolekülen eingesetzt werden können.

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Section: Staudinger-ligation Von Aziden Mit Triarylphosphanenunclassified

Bioorthogonale Chemie – oder: in einem Meer aus Funktionalität nach Selektivität fischen

2009

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“…27 Reduction of azido 14 into amino 15 was achieved using a dithiothreitol (DTT)-mediated reduction. 27,28 The DTT-mediated reduction is normally performed in aqueous solution at near neutral pH and room temperature. This reaction is thus ideal for reducing polar and unstable molecules, for example, the 8-azido-nucleotides in our case.…”

Section: Chemistrymentioning

confidence: 99%

“…The product eluted with a gradient of 0-30% MeCN against 0.05 M TEAB buffer. The appropriate fractions were collected and evaporated, and the resulting residue was co-evaporated with MeOH (3×) to give the title compound 17 in triethylammonium salt (77 mg, 55% (27). To a solution of 8-phenyl-AMP triethylammonium salt (55 mg, 95 µmol) in dry DMSO (0.4 mL) was added triphenylphosphine (113 mg, 431 µmol), morpholine (100 µL, 1.14 mmol), and dipyridyl disulfide (95 mg, 431 µmol).…”

Section: -Methoxy-2′-deoxy-nicotinamide Adenine Dinucleotide (23 8-mentioning

confidence: 99%

2′-Deoxy Cyclic Adenosine 5′-Diphosphate Ribose Derivatives: Importance of the 2′-Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives

et al. 2008

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The structural features needed for antagonism at the cyclic ADP-ribose (cADPR) receptor are unclear. Chemoenzymatic syntheses of novel 8-substituted 2′-deoxy-cADPR analogues, including 8-bromo-2′-deoxycADPR 7, 8-amino-2′-deoxy-cADPR 8, 8-O-methyl-2′-deoxy-cADPR 9, 8-phenyl-2′-deoxy-cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are reported, including improved syntheses of established antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3. Aplysia californica ADP-ribosyl cyclase tolerates even the bulky 8-phenyl-nicotinamide adenine 5′-dinucleotide as a substrate. Structure-activity relationships of 8-substituted cADPR analogues in both Jurkat T-lymphocytes and sea urchin egg homogenate (SUH) were investigated. 2′-OH Deletion decreased antagonistic activity (at least for the 8-amino series), showing it to be an important motif. Some 8-substituted 2′-deoxy analogues showed agonist activity at higher concentrations, among which 8-bromo-2′-deoxy-cADPR 7 was, unexpectedly, a weak but almost full agonist in SUH and was membranepermeant in whole eggs. Classical antagonists 2 and 3 also showed previously unobserved agonist activity at higher concentrations in both systems. The 2′-OH group, without effect on the Ca 2+

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“…In all cases, the major peak was consistent with the expected molecular mass of the full-length peptide, whereas a minor peak observed in the P1-Aha-F lac spectrum (Figure 1 C, indicated by asterisk) was assigned to the full-length peptide with the amino group, and was presumably generated by the dithiothreitol reduction of the azide side chain. [37] The peptide expression directed by the reprogrammed codons thus successfully yielded the expected full-length peptide.…”

Section: Resultsmentioning

confidence: 99%

Ribosomal Synthesis of Peptides with C‐Terminal Lactams, Thiolactones, and Alkylamides

et al. 2009

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All change at the C terminus: We have established a novel methodology for the ribosomal synthesis of peptides featuring C-terminal cyclization and various modifications, including macrocyclization, by making use of genetic code reprogramming. The C-terminal amide modification of linear and cyclic peptides should enhance their physiological stabilities, and open up the possibility of developing new drug-like peptides. The C terminus of a peptide expressed by the translation apparatus generally ends in a carboxylate group. On the other hand, the C termini of some naturally occurring peptides have amide moieties instead of carboxylates, which are believed to give better biostability. Here, we describe a new strategy for the ribosomal synthesis of peptides featuring C-terminal lactam, thiolactone, and alkylamide units. The method was based on the concept of genetic code reprogramming involving the flexizymes (flexible tRNA acylation ribozymes) and the PURE (peptide synthesis using recombinant elements) system, in which vacant codons are reassigned to nonproteinogenic amino acids; this enabled us to convert the C termini of peptides into the above functionalities. We have also applied this method to the synthesis of a macrocyclic peptide closed by an amide bond formed between a lysine side chain and the peptide C terminus. This method thus offers us new opportunities to express various peptides with C-terminal modifications as well as macrocyclic peptides using the translation apparatus, and potentially to accelerate the discovery of peptidic drugs designed for various therapeutic targets.

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The reaction between thiols and 8-azidoadenosine derivatives

Abstract: Thiols react at room temperature in dilute solution with 8-azidoadenosine and its nucleotides to give the corresponding 8-aminoadenosine derivatives. The reaction which takes place in the dark is base-catalysed and is particularly rapid when dithiols, e.g. dithiothreitol are used.

Cited by 107 publications

References 8 publications

Bioorthogonale Chemie – oder: in einem Meer aus Funktionalität nach Selektivität fischen

Bioorthogonale Chemie – oder: in einem Meer aus Funktionalität nach Selektivität fischen

2′-Deoxy Cyclic Adenosine 5′-Diphosphate Ribose Derivatives: Importance of the 2′-Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives

Ribosomal Synthesis of Peptides with C‐Terminal Lactams, Thiolactones, and Alkylamides

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