3-Nitro-2-pyridinesulfenyl-mediated solid-phase disulfide ligation in the synthesis of disulfide bond-containing cyclic peptides

Taguchi, Akihiro; Fukumoto, Kentarou; Asahina, Yuya; Kajiyama, Akihiro; Shimura, Shunsuke; Hamada, Keisuke; Takayama, Kentaro; Yakushiji, Fumika; Hojo, Hironobu; Hayashi, Yoshio

doi:10.1039/c5ob00030k

Cited by 19 publications

(22 citation statements)

References 18 publications

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“…Npys‐OMe 3 a is a stable yellow crystalline compound, which can be stored under shelf conditions for at least six months ( 1 H NMR spectra and Figure S1 in the Supporting Information). In addition, as shown in Scheme B, by using solid‐phase supported Npys‐OMe ( 5 ), 6‐(benzylthio)‐5‐nitronicotinyl ( 4 ) was synthesized on a resin based on a polyethylene glycol ChemMatrix ® resin with swelling properties in both aqueous and organic solvents, and treated with 2 % (v/v) SO 2 Cl 2 /1,2‐DCE in the presence of pyridine to activate the resin‐bound compound as its sulfenyl chloride. Then, after the resin was washed with ice‐cooled CH 2 Cl 2 and dried under a gentle stream of N 2 , it was mixed with 30 % (v/v) DIPEA/MeOH and stirred by vortex mixing for 1.5 h and then filtered and washed with CH 2 Cl 2 and MeOH (five and three times, respectively).…”

Section: Resultsmentioning

confidence: 99%

“…This affords au seful strategy for the synthesis of peptides containing multiple disulfides. [19] In our efforts to develop innovativeN pys chemistry, [20,21] directed towards disulfide bond formation, we were interested in ac ategory of the Npys derivatives, 3-nitro-2-pyridinesulfenate alkoxides (Npys-OR). As originally reported by Matsueda et al, [22] these are prepared by coupling Npys-Cl with various alcohols in the presence of ab ase.…”

Section: Introductionmentioning

confidence: 99%

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3‐Nitro‐2‐pyridinesulfenates as Efficient Solution‐ and Solid‐Phase Disulfide Bond Forming Agents

Taguchi

Kobayashi

Kotani

et al. 2017

Chemistry A European J

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In this paper, a new disulfide-forming agent based on the finding that alkoxy 3-nitro-2-pyridinesulfenates (Npys-OR) can oxidize thiol groups is reported. Methyl 3-nitro-2-pyridinesulfenate (Npys-OMe), which is easily prepared from 3-nitro-2-pyridinesulfenyl chloride in a one-step reaction and has a reduction peak potential (E ) of -0.541 V versus Ag/AgCl, produces the cyclic nonapeptide oxytocin from its linear form in good yield (92 %) with minimal oligomer formation. Npys-OMe in the solid phase also demonstrated excellent results in oxytocin synthesis. Other disulfide-containing peptides, such as α-human atrial natriuretic peptide and α-conotoxin ImI, were also successfully synthesized. During these syntheses, no side reactions of methionine (Met) and tryptophan (Trp) residues or the S-acetamidomethyl (Acm) protecting group were detected. These results suggested that Npys-OMe or its solid-phase analog provides a new strategy for regioselective disulfide bond formation to assist the synthesis of complex disulfide-rich peptides.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3‐Nitro‐2‐pyridinesulfenates as Efficient Solution‐ and Solid‐Phase Disulfide Bond Forming Agents

Taguchi

Kobayashi

Kotani

et al. 2017

Chemistry A European J

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“…Namely, sulfide derivative 6 was reacted in acetonitrile with activated solid-supported disulfide coupling reagent 7, which was prepared from its benzylsulfide form with 2% sulfuryl chloride in 1,2-dichloroethane. 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 It has been reported that the Z33 peptide has a propensity to form an α-helix and bind to the Fc-region of human IgG 1 by the helix-loop-helix structure 17, 27 ( Figure S1). In the circular dichroism (CD) spectra of synthesized compounds, peptide 9 with an additional Cys-Gly sequence at the N-terminus shows almost the same spectral pattern with an α-helix as 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34...…”

Section: Resultsmentioning

confidence: 99%

“…This reaction was performed on the basis of the previous reaction conditions. 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 24 A375 cells were cultured in DMEM containing 10% FBS. Herceptin resistant SKBR-3 cells were cultured in McCoy's 5A containing 10% FBS and 8 µg/mL of Herceptin.…”

Section: Synthesis Of Hybrid Molecule 10 (Plinabulin-ss-z33) By a Solmentioning

confidence: 99%

Novel Hybrid Compound of a Plinabulin Prodrug with an IgG Binding Peptide for Generating a Tumor Selective Noncovalent-Type Antibody–Drug Conjugate

Muguruma¹,

Yakushiji²,

Kawamata³

et al. 2016

Bioconjugate Chem.

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Although several approaches for making antibody-drug conjugates (ADC) have been developed, it has yet to be reported that an antibody binding peptide such as Z33 from protein A is utilized as the pivotal unit to generate the noncovalent-type ADC (NC-ADC). Herein we aim to establish a novel probe for NC-ADC by synthesizing the Z33-conjugated antitumor agent, plinabulin. Due to the different solubility of two components, including hydrophobic plinabulin and hydrophilic Z33, an innovative method with a solid-supported disulfide coupling reagent is required for the synthesis of the target compounds with prominent efficiency (29% isolated yield). We demonstrate that the synthesized hybrid exhibits a binding affinity against the anti-HER2 antibody (Herceptin) and the anti-CD71 antibody (6E1) (Kd = 46.6 ± 0.5 nM and 4.5 ± 0.56 μM, respectively) in the surface plasmon resonance (SPR) assay. In the cell-based assays, the hybrid provides a significant cytotoxicity in the presence of Herceptin against HER2 overexpressing SKBR-3 cells, but not against HER2 low-expressing MCF-7 cells. Further, it is noteworthy that the hybrid in combination with Herceptin induces cytotoxicity against Herceptin-resistant SKBR-3 (SKBR-3HR) cells. Similar results are obtained with the 6E1 antibody, suggesting that the synthesized hybrid can be widely applicable for NC-ADC using the antibody of interest. In summary, a series of evidence presented here strongly indicate that NC-ADCs have high potential for the next generation of antitumor agents.

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“…These latest developments around solid phase reagents led to the synthesis of a universal disulfide bond formation reagent that proved to be particularly useful for disulfide formation in peptides . After chlorosulfenylation, the aforementioned benzylsulfide Npys resin reacted with a tert ‐butyl‐protected thiol‐containing peptide A to form the corresponding active disulfide.…”

Section: Introductionmentioning

confidence: 99%

The 3‐nitro‐2‐pyridinesulfenyl group: synthesis and applications to peptide chemistry

Rentier

Fukumoto

Taguchi

et al. 2017

Journal of Peptide Science

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The 3-nitro-2-pyridinesulfenyl chloride, commonly abbreviated as Npys-Cl, was among the first stable heterocyclic sulfenyl halides to be isolated. After its discovery, the Npys group was widely used as a protecting group for the amines, alcohols and thiols. Herein, we have reviewed some of the aspects of the Npys-Cl moiety, and its most promising recent uses are summarized, from the stability of the Npys protection of amines, hydroxyls and thiols and removal conditions for potential applications in peptide synthesis, to one of its most successful applications for the formation of mixed disulfides. Indeed, Npys protects thiols and acts as an activator for disulfide bond formation, thereby facilitating thiol/disulfide exchange to the corresponding disulfides. The selectivity and mild reaction conditions opened up a wide range of applications in chemical biology as well. Finally, some of the most recent developments regarding the synthesis and applications of solid-phase Npys derivatives are discussed. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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3-Nitro-2-pyridinesulfenyl-mediated solid-phase disulfide ligation in the synthesis of disulfide bond-containing cyclic peptides

Cited by 19 publications

References 18 publications

3‐Nitro‐2‐pyridinesulfenates as Efficient Solution‐ and Solid‐Phase Disulfide Bond Forming Agents

3‐Nitro‐2‐pyridinesulfenates as Efficient Solution‐ and Solid‐Phase Disulfide Bond Forming Agents

Novel Hybrid Compound of a Plinabulin Prodrug with an IgG Binding Peptide for Generating a Tumor Selective Noncovalent-Type Antibody–Drug Conjugate

The 3‐nitro‐2‐pyridinesulfenyl group: synthesis and applications to peptide chemistry

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