Piperazine and DBU: a safer alternative for rapid and efficient Fmoc deprotection in solid phase peptide synthesis

Ralhan, Krittika; KrishnaKumar, V. Guru; Gupta, Sharad

doi:10.1039/c5ra23441g

Cited by 51 publications

(53 citation statements)

References 26 publications

(40 reference statements)

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“…Solution-phase Fmoc-cleavage of Fmoc-Gly-OH was performed to obtain a calibration curve for the UV absorbance at 301 nm vs. the dibenzofulvene-piperidine adduct concentration. 23 In the present work, the loading capacity of the 2-CTC resin was adjusted to a lower level than had been previously reported (0.5-0.8 mmol/g) since a higher loading density might increase the coupling of both the amino groups in Jeffamine to the 2-CTC resin. 21,22 In order to evaluate the quantity of loaded Jeffamine to the resin, the coupling reaction was performed with various eq.…”

Section: Resultsmentioning

confidence: 93%

Efficient Synthesis and Characterization of Monoprotected Symmetrical Poly(Ethylene Glycol) Diamine

Jeong

Youn

Nam

et al. 2017

Bulletin Korean Chem Soc

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Solid-phase synthesis of monoprotected poly(ethylene glycol) (PEG) diamine is demonstrated. 2-Chlorotrityl chloride (2-CTC) resin was used as a solid support for inducing monofunctionalization using excess PEG diamine. Fmoc-monoprotected PEG was prepared from 2-CTC resin and fully characterized by high-performance liquid chromatography and electrospray ionization mass spectrometry. We envision that this strategy will provide an efficient method of preparing various kinds of heterobifunctional PEG molecules without a need for further purification steps.

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Section: Resultsmentioning

confidence: 93%

Efficient Synthesis and Characterization of Monoprotected Symmetrical Poly(Ethylene Glycol) Diamine

Jeong

Youn

Nam

et al. 2017

Bulletin Korean Chem Soc

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“…Thus, we assessed the relative efficiency of Fmoc-deprotection cocktails, which are utilized for the synthesis of thioamidated peptides by monitoring the HPLC chromatogram of the globally deprotected peptide 8. 25,43 Irrespective of the cocktail used, we note that longer exposure to the thioamidated peptide leads to increased epimerization ( Table 2).…”

Section: Resultsmentioning

confidence: 94%

“…Therefore, toward the solid‐phase synthesis of a thiopeptide derived from the GB1 protein ( 8 ), we tested the performance of commonly used Fmoc‐deprotection cocktails (Table 2) and a cocktail containing 2% DBU + 5% piperazine that was reported to outperform 20% piperidine in terms of Fmoc‐deprotection kinetics. Thus, we assessed the relative efficiency of Fmoc‐deprotection cocktails, which are utilized for the synthesis of thioamidated peptides by monitoring the HPLC chromatogram of the globally deprotected peptide 8 25,43 …”

Section: Resultsmentioning

confidence: 99%

Convenient synthesis of thioamidated peptides and proteins

Khatri

Bhat

Chatterjee

2020

Journal of Peptide Science

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The unique physicochemical properties of a thioamide bond, which is an ideal isostere of an amide bond, have not been fully exploited because of the tedious synthesis of thionated amino acid building blocks. Here, we report a purification‐free and highly efficient synthesis of thiobenzotriazolides of Fmoc‐protected and orthogonally protected 20 naturally occurring amino acids including asparagine, glutamine, and histidine. The near‐quantitative conversion to the respective thioamidated peptides on solid support demonstrates the robustness of the synthetic route. Furthermore, the unaltered incorporation efficiency of thiobenzotriazolides from their stock solution till 48 h suggests their compatibility toward automated peptide synthesis. Finally, utilizing an optimized cocktail of 2% DBU + 5% piperazine for fast Fmoc‐deprotection, we report the synthesis of a thioamidated Pin1 WW domain and thioamidated GB1 directly on solid support.

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“…Addition of 1 % formic acid to this combination prevented aspartimide formation. [35] Interestingly, sodium azide in DMF has been shown to cleanly remove the Fmoc group without causing aspartimide formation or racemization. However, the need for conditions involving elevated temperature and long reaction times together with the known explosive potential of the sodium azide salt obviously limits its usefulness.…”

Section: N a -Fmoc Deprotection -The Early Studiesmentioning

confidence: 99%

The 9-Fluorenylmethoxycarbonyl (Fmoc) Group in Chemical Peptide Synthesis – Its Past, Present, and Future

Li¹,

O'Brien-Simpson²,

Hossain³

et al. 2020

Aust. J. Chem.

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The chemical formation of the peptide bond has long fascinated and challenged organic chemists. It requires not only the activation of the carboxyl group of an amino acid but also the protection of the N a -amino group. The more than a century of continuous development of ever-improved protecting group chemistry has been married to dramatic advances in the chemical synthesis of peptides that, itself, was substantially enhanced by the development of solid-phase peptide synthesis by R. B. Merrifield in the 1960s. While the latter technology has continued to undergo further refinement and improvement in both its chemistry and automation, the development of the base-labile 9-fluorenylmethoxycarbonyl (Fmoc) group and its integration into current synthesis methods is considered a major landmark in the history of the chemical synthesis of peptides. The many beneficial attributes of the Fmoc group, which have yet to be surpassed by any other N a -protecting group, allow very rapid and highly efficient synthesis of peptides, including ones of significant size and complexity, making it an even more valuable resource for research in the post-genomic world. This review charts the development and use of this N a -protecting group and its adaptation to address the need for more green chemical peptide synthesis processes.

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Piperazine and DBU: a safer alternative for rapid and efficient Fmoc deprotection in solid phase peptide synthesis

Abstract: We demonstrate PolyAla synthesis using 5% piperazine + 2% DBU, which significantly reduces deletion products arising due to incomplete Fmoc-deprotection and can be used for deletion-free assembly of aggregation prone difficult peptides.

Cited by 51 publications

References 26 publications

Efficient Synthesis and Characterization of Monoprotected Symmetrical Poly(Ethylene Glycol) Diamine

Efficient Synthesis and Characterization of Monoprotected Symmetrical Poly(Ethylene Glycol) Diamine

Convenient synthesis of thioamidated peptides and proteins

The 9-Fluorenylmethoxycarbonyl (Fmoc) Group in Chemical Peptide Synthesis – Its Past, Present, and Future

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