Solid‐Phase Synthesis of Hybrid Urea Oligomers Containing Conservative Thiourea Mutations

Antunes, Stéphanie; Douat, Céline; Guichard, Gilles

doi:10.1002/ejoc.201600177

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…This modification was introduced to facilitate access of the corresponding oligourea using Boc chemistry by avoiding the need for the final HF cleavage of the resin. The solid-phase synthesis (SPS) using Boc chemistry is particularly robust, allowing the preparation of aliphatic oligoureas and related hybrids with good purities and yields. − Here, the elongation of CPFs using Boc-protected activated monomers A was preferred over the use of azido building blocks and TFA-labile resins, also because access to the activated His-type monomer required for such CPF sequences remains limited to its N -Boc protected version . Our new strategy relies on the use of a resin equipped with a cystamine linker that can be cleaved under reductive conditions to release the CPF with a terminal thiol-function.…”

Section: Results and Discussionmentioning

confidence: 99%

Hybrid Cell-Penetrating Foldamer with Superior Intracellular Delivery Properties and Serum Stability

et al. 2019

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Sequence specific molecules with high folding ability (i.e. foldamers) can be used to precisely control the distribution and projection of side chains in space and have recently been introduced as tailored systems for delivering nucleic acids into cells. Designed oligourea sequences with an amphipathic distribution of Arg-and His-type residues were shown to form tight complexes with plasmid DNA, and to effectively promote the release of DNA from the endosomes. Herein, we report the synthesis of new cell-penetrating foldamer sequences in which the foldamer segment is conjugated via a reducible disulfide bond to a ligand that binds cell-surface expressed nucleoproteins with the idea that this system could facilitate both assemblies with nucleic acids and cell entry. This new system was evaluated for delivery of DNA in several cell lines and was found to compare favorably with all comparators tested (DOTAP and b-PEI as well as a number of known cell penetrating peptides) in various cell lines and particularly in culture medium containing up to 50% of serum. These results suggest that this dual molecular platform which is long lasting and non-cytotoxic could be of practical use for in vivo applications.

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Section: Results and Discussionmentioning

confidence: 99%

Hybrid Cell-Penetrating Foldamer with Superior Intracellular Delivery Properties and Serum Stability

et al. 2019

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“…We next applied this postelongation guanidinylation method to the solid support with the aim to speed the access to more functionalized and biologically relevant sequences. We have recently reported an efficient solid-phase methodology to prepare oligo(thio)ureas on TFA-labile resins . This optimized solid-phase synthesis (SPS) protocol was applied here to synthesize a resin-bound 8-mer oligo(thiourea/amide/urea) hybrid on Rink-amide resin ( 20 R ) as a direct precursor for the guanidinylation steps (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Postelongation Strategy for the Introduction of Guanidinium Units in the Main Chain of Helical Oligourea Foldamers

et al. 2018

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The synthesis of hybrid urea-based foldamers containing isosteric guanidinium linkages at selected positions in the sequence is described. We used a postelongation approach whereby the guanidinium moiety is introduced by direct transformation of a parent oligo(urea/thiourea) foldamer precursor. The method involves activation of the thiourea by treatment with methyl iodide and subsequent reaction with amines. To avoid undesired cyclization with the preceding urea moiety, resulting in heterocyclic guanidinium formation in the main chain, the urea unit preceding the thiourea unit in the sequence was replaced by an isoatomic and isostructural γ-amino acid. The approach was extended to solid-phase techniques to accelerate the synthesis of longer and more functionalized sequences. Under optimized conditions, an octamer hybrid oligomer incorporating a central guanidinium linkage was obtained in good overall yield and purity. This work also reports data related to the structural consequences of urea by guanidinium replacements in solution and reveals that helical folding is substantially reduced in oligomers containing a guanidinium group.

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“…Thus far, the best conditions identified for on-resin reduction of azido-terminated oligoureas involve the use of trimethylphosphine with microwave assistance. This method is compatible with automation and parallel synthesis and is now routinely used in our laboratory to prepare oligoureas and related peptide-oligourea hybrids (Antunes, Douat, & Guichard, 2016;Cussol et al, 2021). The detailed synthetic procedures are reported in section 5.3.…”

Section: Solid Phase Synthesis Of Oligoureasmentioning

confidence: 99%

Urea based foldamers

Yoo

Dolain

et al. 2021

Methods in Enzymology

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Solid‐Phase Synthesis of Hybrid Urea Oligomers Containing Conservative Thiourea Mutations

Cited by 6 publications

References 35 publications

Hybrid Cell-Penetrating Foldamer with Superior Intracellular Delivery Properties and Serum Stability

Hybrid Cell-Penetrating Foldamer with Superior Intracellular Delivery Properties and Serum Stability

Postelongation Strategy for the Introduction of Guanidinium Units in the Main Chain of Helical Oligourea Foldamers

Urea based foldamers

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