Tea Bags for Fmoc Solid-Phase Peptide Synthesis: An Example of Circular Economy

Guzmán, Fanny; Gauna, Adriana; Román, Tanya; Luna, Omar; Álvarez, Claudio; Pareja-Barrueto, Claudia; Mercado, Luís; Alberício, Fernando; Cárdenas, Constanza

doi:10.3390/molecules26165035

Cited by 27 publications

(23 citation statements)

References 23 publications

(24 reference statements)

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“…Next, using the CTC resin and Trt as the protecting group for Cys and the peptide Boc-Leu-Ala-Cys(Trt)-O-CT-resin as a model, several secondary cyclic amines, namely, piperidine (PP), 4-methylpiperidine (4 MP), , piperazine (PZ), pyrrolidine (PY), and morpholine (MOP), , were studied (Figure ). Furthermore, in some cases, an acid rectifier, OxymaPure, was added to achieve a buffer impact, which has been demonstrated to reduce the formation of other side products such as aspartimides and δ-lactams. − …”

Section: Resultsmentioning

confidence: 99%

Solid-Phase Synthesis of C-Terminus Cysteine Peptide Acids

Mthembu

Chakraborty

Schönleber

et al. 2022

Org. Process Res. Dev.

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Cysteine (Cys) is a key amino acid in many therapeutic peptides. For research and industrial purposes, solid-phase peptide synthesis is the method of choice for the preparation of most peptides. The solid-phase synthesis of C-terminal Cys peptide acids is problematic because it is accompanied by a side reaction, namely, the abstraction of α-H from the Cys residue, which leads to the formation of three side products: the epimer and two N-piperidinyl-Ala epimer peptides. Here, we used a chlorotrityl chloride resin to conduct a rational and in-depth study of this side reaction. The following variables were examined: removal of the fluorenylmethoxycarbonyl (Fmoc) group by different bases, the presence or absence of an acid rectifier for buffering the base, and thiol side-chain protection. In conclusion, the use of Fmoc-Cys protected with tetrahydropyran (Thp) and 4-methoxytrityl (Mmt) along with 30% 4-methylpiperidine in 0.5 M OxymaPure-DMF for Fmoc removal assures minimization of the side reaction, as demonstrated in a model peptide and confirmed for the elongation of somatostatin.

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Section: Resultsmentioning

confidence: 99%

Solid-Phase Synthesis of C-Terminus Cysteine Peptide Acids

Mthembu

Chakraborty

Schönleber

et al. 2022

Org. Process Res. Dev.

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“…Solid-phase synthesis also generates a significant amount of waste with most protocols calling for repeated washing following acylation and amination, requiring approximately 20 mL of DMF washes with each monomer addition . Cárdenas and co-workers addressed waste generation in peptide synthesis by implementing a circular economy strategy that recycled the final two DMF washes from a coupling cycle as the first two washes in the next cycle . This protocol allowed for a 25–30% reduction in DMF consumption, minimizing costs and waste production without compromising the purity of the synthesized peptides.…”

Section: Discussionmentioning

confidence: 99%

“…13 Caŕdenas and coworkers addressed waste generation in peptide synthesis by implementing a circular economy strategy that recycled the final two DMF washes from a coupling cycle as the first two washes in the next cycle. 123 This protocol allowed for a 25− 30% reduction in DMF consumption, minimizing costs and waste production without compromising the purity of the synthesized peptides. While the recycling of washes can be easily adapted to manual peptoid synthesis, this concept should also be compatible with automated protocols.…”

Section: Discussionmentioning

confidence: 99%

A Field Guide to Optimizing Peptoid Synthesis

2022

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N-Substituted glycines (peptoids) are a class of peptidomimetic molecules used as materials for health, environmental, and drug delivery applications. Automated solid-phase synthesis is the most widely used approach for preparing polypeptoids, with a range of published protocols and modifications for selected synthetic targets. Simultaneously, emerging solutionphase syntheses are being leveraged to overcome limitations in solid-phase synthesis and access high-molecular weight polypeptoids. This Perspective aims to outline strategies for the optimization of both solid-and solution-phase synthesis, provide technical considerations for robotic synthesizers, and offer an outlook on advances in synthetic methodologies. The solid-phase synthesis sections explore steps for protocol optimization, accessing complex side chains, and adaptation to robotic synthesizers; the sections on solution-phase synthesis cover the selection of initiators, side chain compatibility, and strategies for controlling polymerization efficiency and scale. This text acts as a "field guide" for researchers aiming to leverage the flexibility and adaptability of peptoids in their research.

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“…Peptide cleavage was carried out with a solution of trifluoroacetic acid, triisopropylsilane, EDT (2,2-(ethylenedioxy)diethanethiol) and water in 92.5:2.5:2.5:2.5 ratio. Reaction products were purified by reverse phase chromatography up to >90% purity 46 , 47 .…”

Section: Methodsmentioning

confidence: 99%

Insights into the equilibrium structure and translocation mechanism of TP1, a spontaneous membrane-translocating peptide

Muñoz-Gacitúa

Guzmán²,

Weiss-López³

2022

Sci Rep

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Crossing the cellular membrane is one of the main barriers during drug discovery; many potential drugs are rejected for their inability to integrate into the intracell fluid. Although many solutions have been proposed to overcome this barrier, arguably the most promising solution is the use of cell-penetrating peptides. Recently, an array of hydrophobic penetrating peptides was discovered via high throughput screening which proved to be able to cross the membrane passively, and although these peptides proved to be effective at penetrating the cell, the details behind the underlying mechanism of this process remain unknown. In this study, we developed a method to find the equilibrium structure at the transmembrane domain of TP1, a hydrophobic penetrating peptide. In this method, we selectively deuterium-label amino acids in the peptidic chain, and employ results of $$^2$$ 2 H-NMR spectroscopy to find a molecular dynamics simulation of the peptide that reproduces the experimental results. Effectively finding the equilibrium orientation and dynamics of the peptide in the membrane. We employed this equilibrium structure to simulate the entire translocation mechanism and found that after the peptide reaches its equilibrium structure, it must undergo a two-step mechanism in order to completely translocate the membrane, each step involving the flip-flop of each arginine residue in the peptide. This leads us to conclude that the RLLR motif is essential for the translocating activity of the peptide.

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Tea Bags for Fmoc Solid-Phase Peptide Synthesis: An Example of Circular Economy

Cited by 27 publications

References 23 publications

Solid-Phase Synthesis of C-Terminus Cysteine Peptide Acids

Solid-Phase Synthesis of C-Terminus Cysteine Peptide Acids

A Field Guide to Optimizing Peptoid Synthesis

Insights into the equilibrium structure and translocation mechanism of TP1, a spontaneous membrane-translocating peptide

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