Efficient Synthesis and Oxidative Folding Studies of Centipede Toxin RhTx

Wang, Jinyan; Dong, Liying; Liu, Ya'ni; Chen, Xitong; Ma, Yan-Nan; Yin, Hao; Du, Shanshan; Qi, Yun‐Kun; Wang, Kewei

doi:10.6023/cjoc202102045

Cited by 11 publications

(9 citation statements)

References 69 publications

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“…The manual synthesis of peptides 1 , 2 , and 3 was carried out under 28°C using the traditional HCTU/DIEA‐based SPPS in a normal air‐bath thermostatic oscillator 38–41 . A total of 160 mg of Fmoc‐protected Rink Amide AM resin (0.32 mmol/g, 1 eq) was swelled in DCM/DMF = 1:1 ( v/v ) solution for 60 min before use.…”

Section: Methodsmentioning

confidence: 99%

“…The manual synthesis of peptides 1, 2, and 3 was carried out under 28 C using the traditional HCTU/DIEA-based SPPS in a normal air-bath thermostatic oscillator. [38][39][40][41] A total of 160 mg of Fmocprotected Rink Amide AM resin (0.32 mmol/g, 1 eq) was swelled in DCM/DMF = 1:1 (v/v) solution for 60 min before use. The Fmoc protecting group was removed by 20% piperidine in DMF (v/v) (twice: 5 min and then 10 min), and the resin was thoroughly washed with DMF and DCM.…”

Section: Solid-phase Synthesis Of Peptides 1 2 Andmentioning

confidence: 99%

“…The purified linear peptides 1, 5, 6, 7, 8, and 9 were folded by the one-step oxidative folding strategy. 33,41,43,44 The linear peptide 1 (23 mg, 30 μM) was dissolved in the folding buffer (pH = 7.5) containing GSH (5 mM), GSSG (0.5 mM), and 0.1-M Tris buffer. The folding process was then conducted at 25 C in air-bath thermostatic oscillator.…”

mentioning

confidence: 99%

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DIC/Oxyma‐based accelerated synthesis and oxidative folding studies of centipede toxin RhTx

Chen

Wang

et al. 2021

Journal of Peptide Science

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Coupling reagents play crucial roles in the iterative construction of amide bonds for the synthesis of peptides and peptide-based derivatives. The novel DIC/Oxyma condensation system featured with the low risk of explosion displayed remarkable abilities to inhibit racemization, along with efficient coupling efficiency in both manual and automated syntheses. Nevertheless, an ideal reaction molar ratio in DIC/Oxyma condensation system and the moderate reaction temperature by manual synthesis remain to be further investigated. Herein, the synthetic efficiencies of different reaction ratios between DIC and Oxyma under moderate reaction temperature were systematically evaluated. The robustness and efficiency of DIC/Oxyma condensation system are validated by the rapid synthesis of linear centipede toxin RhTx. Different folding strategies were applied for the construction of disulfide bridges in RhTx, which was further confirmed in assays of circular dichroism and patch-clamp electrophysiology evaluation. This work establishes the DIC/Oxyma-based accelerated synthesis of peptides under moderate condensation conditions, which is especially useful for the manual synthesis of peptides. Besides, the strategy presented here provides robust technical supports for the large-scale synthesis and oxidative folding of RhTx.

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Section: Methodsmentioning

confidence: 99%

Section: Solid-phase Synthesis Of Peptides 1 2 Andmentioning

confidence: 99%

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DIC/Oxyma‐based accelerated synthesis and oxidative folding studies of centipede toxin RhTx

Chen

Wang

et al. 2021

Journal of Peptide Science

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“…[71][72][73][74][75][76][77][78][79] They have found increasing applications in the synthesis of various proteins and peptides, including posttranslationally modified proteins, customdesigned proteins, protein-based probes, membrane proteins, and cyclic peptides etc. [80][81][82][83][84] Different from the linear synthetic strategy developed by the Payne group, the Li group achieved the first convergent total synthesis of teixobactin through Ser ligation mediated "6 + 5" strategy (Figure 13). 67,85 Generally, the linear hexapeptide (1-6) 39…”

Section: The First Total Synthesis Of Teixobactin By the Payne Groupmentioning

confidence: 99%

“…Natural chemical ligation (NCL) and modified versions of NCL are widely used in synthetic protein chemistry by different labs 71–79 . They have found increasing applications in the synthesis of various proteins and peptides, including posttranslationally modified proteins, custom‐designed proteins, protein‐based probes, membrane proteins, and cyclic peptides etc 80–84 . Different from the linear synthetic strategy developed by the Payne group, the Li group achieved the first convergent total synthesis of teixobactin through Ser ligation mediated “6 + 5” strategy (Figure 13).…”

Section: Total Synthesis Of Teixobactinmentioning

confidence: 99%

Discovery, synthesis, and optimization of teixobactin, a novel antibiotic without detectable bacterial resistance

Tang

Wang

et al. 2022

Journal of Peptide Science

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Discovering new antibiotics with novel chemical scaffolds and antibacterial mechanisms presents a challenge for medicinal scientists worldwide as the ever‐increasing bacterial resistance poses a serious threat to human health. A new cyclic peptide‐based antibiotic termed teixobactin was discovered from a screen of uncultured soil bacteria through iChip technology in 2015. Teixobactin exhibits excellent antibacterial activity against all the tested gram‐positive pathogens and Mycobacterium tuberculosis, including drug‐resistant strains. Given that teixobactin targets the highly conserved lipid II and lipid III, which induces the simultaneous inhibition of both peptidoglycan and teichoic acid synthesis, the emergence of resistance is considered to be rather difficult. The novel structure, potent antibacterial activity, and highly conservative targets make teixobactin a promising lead compound for further antibiotic development. This review provides a comprehensive treatise on the advances of teixobactin in the areas of discovery processes, antibacterial activity, mechanisms of action, chemical synthesis, and structural optimizations. The synthetic methods for the key building block l‐allo‐End, natural teixobactin, representative teixobactin analogs, as well as the structure–activity relationship studies will be highlighted and discussed in details. Finally, some insights into new trends for the generation of novel teixobactin analogs and tips for future work and directions will be commented.

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Efficient synthesis and anticancer evaluation of spider toxin peptide LVTX-8-based analogues with enhanced stability

Chi

Jia

Yin

et al. 2023

Bioorganic Chemistry

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Efficient Synthesis and Oxidative Folding Studies of Centipede Toxin RhTx

Cited by 11 publications

References 69 publications

DIC/Oxyma‐based accelerated synthesis and oxidative folding studies of centipede toxin RhTx

DIC/Oxyma‐based accelerated synthesis and oxidative folding studies of centipede toxin RhTx

Discovery, synthesis, and optimization of teixobactin, a novel antibiotic without detectable bacterial resistance

Efficient synthesis and anticancer evaluation of spider toxin peptide LVTX-8-based analogues with enhanced stability

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