Studies on amino acids and peptides-III. 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, , as a new racemization free coupling reagent in peptide synthesis

Pedersen, U.; Thorsen, M.; El-Khrisy, Ezz El-Din A.M.; Clausen, K.; Lawesson, S.‐O.

doi:10.1016/0040-4020(82)80104-x

Cited by 24 publications

(11 citation statements)

References 5 publications

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“…Lawesson’s reagent). 11,28 Such treatments suffer from exceedingly poor site-selectivity and are not suitable for the modification of larger peptides. 29,30 An alternative strategy entails the thiolysis of an oxazoline heterocycle using H 2 S ( i.e.…”

Section: Resultsmentioning

confidence: 99%

Insights into the Mechanism of Peptide Cyclodehydrations Achieved through the Chemoenzymatic Generation of Amide Derivatives

Dunbar

Mitchell

2013

J. Am. Chem. Soc.

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Current strategies for generating peptides and proteins bearing amide carbonyl derivatives rely on solid-phase peptide synthesis for amide functionalization. Although such strategies have been successfully implemented, technical limitations restrict both the length and sequence of the synthetic fragments. Herein we report the repurposing of a thiazole/oxazole-modified microcin (TOMM) cyclodehydratase to site-specifically install amide backbone labels onto diverse peptide substrates, a method we refer to as azoline-mediated peptide backbone labeling (AMPL). This convenient chemoenzymatic strategy can generate both thioamides and amides with isotopically labeled oxygen atoms. Moreover, we demonstrate the first leader peptide-independent activity of a TOMM synthetase, circumventing the requirement that sequences of interest be fused to a leader peptide for modification. Through bioinformatics-guided site-directed mutagenesis, we also convert a strictly dehydrogenase-dependent TOMM azole synthetase into an azoline synthetase. This vastly expands the spectrum of substrates modifiable by AMPL by allowing any in vitro reconstituted TOMM synthetase to be employed. To demonstrate the utility of AMPL for mechanistic enzymology studies, an 18O-labeled substrate was generated to provide direct evidence that cyclodehydrations in TOMMs occur through the phosphorylation of the carbonyl oxygen preceding the cyclized residue. Furthermore, we demonstrate that AMPL is a useful tool for establishing the location of azolines both on in vitro modified peptides and azoline-containing natural products.

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Section: Resultsmentioning

confidence: 99%

Insights into the Mechanism of Peptide Cyclodehydrations Achieved through the Chemoenzymatic Generation of Amide Derivatives

Dunbar

Mitchell

2013

J. Am. Chem. Soc.

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“…[h] [ α ]${{{22\hfill \atop {\rm D}\hfill}}}$ =−19.4 ( c =2.19, EtOH); reference [19]: −19.80 19. [i] [ α ]${{{22\hfill \atop {\rm D}\hfill}}}$ =−60.4 ( c =2.43, AcOEt); reference [20]: −60.4 20…”

Section: Resultsmentioning

confidence: 99%

“…20 :12, 20 Z‐ L ‐Pro‐Gly‐OEt: 1 H NMR (CDCl 3 ): δ =7.44–7.22 (m, 5 H, Ph), 7.09 (br s, 1 H, 2‐NH in one of rotamers), 6.48 (br s, 1 H, 2‐NH in one of rotamers), 5.12 (d, J =12.4 Hz, 1 H, Bn), 5.04 (d, J =12.4 Hz, 1 H, Bn), 4.40–4.20 (br m, 1 H, 2′‐H), 4.10 (q, J =7.1 Hz, 2 H, EtO), 4.06–3.42 (br m, 4 H, 2‐H, 5′‐H), 2.36–1.85 (m, 4 H, 3′‐H, 4′‐H), 1.27 ppm (t, J =7.1 Hz, 3 H, EtO); 13 C NMR (CDCl 3 ): δ =171.9 (C1′), 169.5 (C1), 155.9 (Z‐C), 136.3 (Ph), 128.3 (Ph), 127.9 (Ph), 127.8 (Ph), 67.1 (Bn), 61.2 (EtO), 60.4 (C2′), 46.9 (C2), 41.2 (C5′), 28.5 (C3′), 24.3 (C4′), 14.0 ppm (EtO).…”

Section: Methodsmentioning

confidence: 99%

4‐(Dimethylamino)pyridine N‐oxide (DMAPO): An Effective Nucleophilic Catalyst in the Peptide Coupling Reaction with 2‐Methyl‐6‐nitrobenzoic Anhydride

Shiina

Ushiyama

Yamada

et al. 2008

Chemistry An Asian Journal

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Various carboxamides or peptides were synthesized from the corresponding carboxylic acids and amines or alpha-amino acids in high yields by the catalysis of 4-(dimethylamino)pyridine N-oxide (DMAPO) with 2-methyl-6-nitrobenzoic anhydride (MNBA). Because the segment-coupling reaction of alpha-amino acids proceeds through the effective activation of the carboxylic acid moieties with DMAPO in the presence of tertiary amines under mild conditions, undesired racemization was hardly observed in the synthesis of oligopeptides such as Z-Gly-Phe-Val-OMe, Z-Phe-Val-Ala-OMe, and Bz-Val-Val-OMe.

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“…This substitution has became easier by the Lawesson's reagent. 202 The thioamide C=S bond ( 1.66 A) is significantly longer when compared to the C = 0 bond Figure 24) the position of the isosteric replacement may influence the conformation by allowing different packing in the crystal. In fact, the latter pseudopeptide investigated maintains a type 111 P-bend conformation stabilized by a 1 c 4 intramolecular H bond, as in the parent peptide, while the former pseudopeptide shows a partially extended conformation with no intramolecular H bond.…”

Section: Peptides Containing the Thloamlde Surrogatementioning

confidence: 98%

X‐ray crystallography of peptides: The contributions of the Italian laboratories

Benedetti

1996

Biopolymers

139

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The review article summarizes the most relevant solid state structural and conformational results obtained in the laboratories involved in Italy in the studies of synthetic and natural peptides by x‐ray diffraction analyses. Some of the topics will include research studies carried out in other European countries, whereas in other cases studies carried out in Italy will be included in other review articles included in this volume. The review deals with peptides containing symmetrically achiral and unsymmetrically chiral Cα,α‐dialkylated glycine residues, peptides containing β‐alanine residues, α,β‐dehydroamino acid residues, and aminosuccinyl residues, peptides containing the thioamide surrogate, heterochiral peptides and several bioactive peptides systems with the proposed relationships between function and structure. © 1996 John Wiley & Sons, Inc.

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Studies on amino acids and peptides-III. 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, , as a new racemization free coupling reagent in peptide synthesis

Cited by 24 publications

References 5 publications

Insights into the Mechanism of Peptide Cyclodehydrations Achieved through the Chemoenzymatic Generation of Amide Derivatives

Insights into the Mechanism of Peptide Cyclodehydrations Achieved through the Chemoenzymatic Generation of Amide Derivatives

4‐(Dimethylamino)pyridine N‐oxide (DMAPO): An Effective Nucleophilic Catalyst in the Peptide Coupling Reaction with 2‐Methyl‐6‐nitrobenzoic Anhydride

X‐ray crystallography of peptides: The contributions of the Italian laboratories

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