Dde-protected PNA monomers, orthogonal to Fmoc, for the synthesis of PNA–peptide conjugates

Bialy, Laurent; Díaz‐Mochón, Juan José; Specker, Edgar; Keinicke, Lise; Bradley, Mark

doi:10.1016/j.tet.2005.06.003

Cited by 29 publications

(36 citation statements)

References 22 publications

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“…The polyamine was added to the resin and the reaction proceeded for 3 h at room temperature. Next, the primary amines were selectively protected using DDE . The secondary amines were protected using di‐tertbutyl‐dicarbonate.…”

Section: Methodsmentioning

confidence: 99%

Developing Polyamine‐Based Peptide Amphiphiles with Tunable Morphology and Physicochemical Properties

Samad

Chhonker

Contreras

et al. 2017

Macromolecular Bioscience

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The ability to tune supramolecular properties such as size, morphology, or metabolic stability is of paramount importance in the field of supramolecular chemistry. Peptide amphiphiles (PAs) are a family of functional self-assembling biomaterials that have garnered widespread attention due to their broad applicability in medicine. PAs are generally comprised of an amino acid sequence connected to lipid tail(s) allowing them to self-assemble into supramolecular structures with diverse morphologies. Herein, this study describes the synthesis of a new class of polyamine-based "hybrid" PAs (PPAs) as novel self-assembling systems. The described molecules possess diverse polyamine head groups with the goal of tuning physicochemical properties. The findings indicate that small changes in the polyamine head groups result in altered PPA morphologies (nanofibers, micelles, nanoworms). The PPAs present a wide range of physicochemical characteristics, show superior resistance to aggregation, a diverse metabolic profile, and varied assembling kinetics. Most of the PPAs do not show toxicity in the human cells lines evaluated. The PPAs described herein hold promising potential as a safe and nontoxic option for drug delivery, targeting, and tissue engineering applications.

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Section: Methodsmentioning

confidence: 99%

Developing Polyamine‐Based Peptide Amphiphiles with Tunable Morphology and Physicochemical Properties

Samad

Chhonker

Contreras

et al. 2017

Macromolecular Bioscience

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“…62 The synthesis of branched peptide-PNA conjugates requires a more flexible strategy, since the PNA and the peptide should be elongated in a truly orthogonal fashion. 63,64 It is desirable that the N-terminal protecting group on PNA monomers PG 1 (Figure 4.1) is stable under the cleavage conditions for the N-terminal protecting group on amino acid monomers (PG N ; usually the Fmoc group) and their acid-labile side-chain protecting groups PG R . At the same time the protecting groups on the nucleobases and on the amino acid sidechains should be cleaved together under the final deprotection conditions.…”

Section: Continuous Synthesismentioning

confidence: 99%

“…Thus, PNA monomers with a 1-(4,4-dimethyl-2,6-dioxacyclohexylidene)ethyl (Dde) protecting group on the N-terminus and Mmt on the nucleobases appears to be fully orthogonal to the commercially available Fmoc amino acid monomers. 63,64 The orthogonality of Dde and Fmoc groups is based on their different mechanisms for deprotection. While Fmoc is cleaved by basic elimination, Dde is removed by treatment with nucleophiles (trans-elimination).…”

Section: Continuous Synthesismentioning

confidence: 99%

Peptide–Peptide Nucleic Acid Conjugates for Modulation of Gene Expression

Fabani

Ivanova

Gait

2008

Therapeutic Oligonucleotides

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“…3 Furthermore, PNA is stable over a wide pH range and is resistant to both nucleases and proteases, 4 making PNA a molecule of choice for gene therapy applications, and also for high-throughput analysis using PNA microarrays, although these have been little explored. [5][6][7][8][9] The orthogonal, solid phase, synthesis of PNA-peptide conjugates using a Dde/Fmoc strategy with Dde/Mmt protected PNA monomers 1-4 (Scheme 1) and Fmoc/ t Bu protected amino acids has been reported previously, [10][11][12][13] however, this approach is time consuming and non-automated, limiting wider applications of PNA in chemistry and biology. Here we report an automated orthogonal microwave synthesis of PNA-peptide conjugates, and illustrate this strategy with the synthesis of two specific receptor-based, cellular binding, PNA-encoded peptide ligands, ArgGly-Asp-12-mer-PNA and Arg-Gly-Glu-12-mer-PNA.…”

mentioning

confidence: 99%

“…Here we report an automated orthogonal microwave synthesis of PNA-peptide conjugates, and illustrate this strategy with the synthesis of two specific receptor-based, cellular binding, PNA-encoded peptide ligands, ArgGly-Asp-12-mer-PNA and Arg-Gly-Glu-12-mer-PNA. 11,12,13 Resin 5 (Scheme 2) and the PNA monomers 1-4 were synthesized according to previously reported procedures, 10 with the sole exception that the coupling of the functionalized nucleobases to the backbone was carried out with solid-supported dicyclohexylcarbodiimide (PS-DCC) rather than conventional DCC. 14,15 PNA-peptide synthesis was carried out in an automated CEM peptide synthesizer.…”

mentioning

confidence: 99%