Efficient Fmoc Group Removal Using Diluted 4-Methylpiperidine: An Alternative for a Less-Polluting SPPS-Fmoc/tBu Protocol

Rodríguez, Verónica; Piñeda, Héctor E.; Ardila, Natalia; Insuasty, Diego; Cárdenas, Karen; Román, Julieth; Urrea, Maribel; Ramírez, David A.; Fierro, Ricardo; Rivera, Zuly; Garcı́a, Javier

doi:10.1007/s10989-019-09865-9

Cited by 10 publications

(7 citation statements)

References 2 publications

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“…Solid-Phase Peptide Synthesis�Fmoc/tBu. Palindromic and modified peptides were manually synthetized using the Fmoc-tBu strategy in accordance to Rodri ́guez et al 40 In brief, rink amide resin (0.46 mEq g −1 ) treated with DCM at room temperature (RT) for 2 h was used as a solid support. Elongation of the sequence was carried through sequential steps of (i) Fmoc group removal under basic conditions, treating the resin or resin−peptide with 2.5% v/v 4-methyl piperidine by 15 min (twice); (ii) Fmoc-amino acid/DCC/6-Cl-HOBt (1:1:1 meq and 5 excess with respect to resin substitution) were dissolved in DMF/DCM mixture (2:1 v/v); then two drops of Triton X-100 were added, and the reaction mixture was gently stirred for 15 min at RT.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

et al. 2023

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Breast cancer is one of the main causes of premature death in women; current treatments have low selectivity, generating strong physical and psychological sequelae. The palindromic peptide R-1-R (RWQWRWQWR) has cytotoxic activity against different cell lines derived from cancer and selectivity against noncancerous cells. To determine if changes in the charge/length of this peptide increase its activity, six peptides were obtained by SPPS, three of them with addition of Arg at the N, C-terminal or both and three with deletion of Arg at the N, C-terminal or both. The cytotoxic and selective activities were evaluated against MCF-7, MDA-MB-231, and MCF-12 cell lines and fibroblast primary cell culture, evidencing that the RR-1-R peptide with the inclusion of Arg in the N-terminal end maintained selectivity and increased cytotoxicity against lines derived from breast cancer. The effect of this addition regarding the type of induced cell death was evaluated by flow cytometry, showing very low rates of necrosis and a significant majority of apoptotic events with activation of both Caspase 8 and Caspase 9. This work allowed us to find a modification that generates a peptide with greater cytotoxic effects and can be considered a promising molecule for other approaches to improve anticancer peptides.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

et al. 2023

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“…Peptides were synthesized using manual solid‐phase peptide synthesis with the Fmoc/ t Bu strategy (SPPS‐Fmoc/ t Bu) [32] . Briefly, Rink amide resin (100 mg, 0.46 meq/g) was used as solid support.…”

Section: Methodsmentioning

confidence: 99%

Designing Chimeric Peptides: A Powerful Tool for Enhancing Antibacterial Activity

Pineda-Castañeda

Huertas-Ortiz

Leal-Castro

et al. 2021

Chemistry & Biodiversity

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Chimeric peptides containing short sequences derived from bovine Lactoferricin (LfcinB) and Buforin II (BFII) were synthetized using solid‐phase peptide synthesis (SPPS) and characterized via reversed‐phase liquid chromatography and mass spectrometry. The chimeras were obtained with high purity, demonstrating their synthetic viability. The chimeras’ antibacterial activity against Gram‐positive and Gram‐negative strains was evaluated. Our results showed that all the chimeras exhibited greater antibacterial activity against the evaluated strains than the individual sequences, suggesting that chemical binding of short sequences derived from AMPs significantly increased the antibacterial activity. For each strain, the chimera with the best antibacterial activity exerted a bacteriostatic and/or bactericidal effect, which was dependent on the concentration. It was found that: (i) the antibacterial activity of a chimera is mainly influenced by the linked sequences, the palindromic motif RLLRRLLR being the most relevant one; (ii) the inclusion of a spacer between the short sequences did not significantly affect the chimera's synthesis process; however, it enhanced its antibacterial activity against Gram‐negative and Gram‐positive strains; on the other hand, (iii) the replacement of Arg with Lys in the LfcinB or BFII sequences improved the chimeras’ synthesis process without significantly affecting their antibacterial activity. These results illustrate the great importance of the synthesis of chimeric peptides for the generation of promising antibacterial peptides.

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“…[39] More recently, Rodriguez and colleagues also confirmed the effectiveness of 4-methylpiperidine but recommended the use of lower concentrations (2.5 % v/v in DMF), which is as effective but has reduced toxicity. [40] The N a -Fmoc Group in 'Green' Chemical Peptide Synthesis Strategies Much recent effort has been devoted by both academia and industry to significantly improve the environmental impact of chemical peptide synthesis. The latter includes substantial amounts of toxic process solvents such as DMF and NMP due to the large number of repetitive chemical steps required to produce a peptide together with intermediate washing.…”

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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Efficient Fmoc Group Removal Using Diluted 4-Methylpiperidine: An Alternative for a Less-Polluting SPPS-Fmoc/tBu Protocol

Cited by 10 publications

References 2 publications

Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines

Designing Chimeric Peptides: A Powerful Tool for Enhancing Antibacterial Activity

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

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