Synthesis of a biologically active triazole-containing analogue of cystatin A through successive peptidomimetic alkyne-azide ligations
| Autor: | Agnès F. Delmas, Vincent Aucagne, Ibai E. Valverde, Gilles Lalmanach, Fabien Lecaille |
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| Přispěvatelé: | Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Azides
MESH: Cell Line Tumor Peptidomimetic Molecular Sequence Data Peptide MESH: Amino Acid Sequence 010402 general chemistry 01 natural sciences Catalysis chemistry.chemical_compound Cell Line Tumor Peptide synthesis Peptide bond Humans Cystatin A Neoplasm Invasiveness [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence MESH: Cystatin A MESH: Cyclization Peptide sequence MESH: Peptidomimetics MESH: Click Chemistry ComputingMilieux_MISCELLANEOUS chemistry.chemical_classification MESH: Humans MESH: Molecular Sequence Data 010405 organic chemistry General Chemistry General Medicine MESH: Neoplasm Invasiveness Triazoles Native chemical ligation Combinatorial chemistry Cathepsins MESH: Azides 0104 chemical sciences chemistry MESH: Triazoles Cyclization Alkynes MESH: Cathepsins Click chemistry Click Chemistry Chemical ligation Peptidomimetics MESH: Alkynes |
| Zdroj: | Angewandte Chemie International Edition Angewandte Chemie International Edition, Wiley-VCH Verlag, 2012, 51 (3), pp.718-22. ⟨10.1002/anie.201107222⟩ |
| ISSN: | 1433-7851 1521-3773 |
| DOI: | 10.1002/anie.201107222⟩ |
| Popis: | Amide surrogates are common in naturally occurring peptides and in synthetic peptides used in therapy. Whereas backbone-engineered proteins are, to date, extremely laborious to produce by genetic means, the advent of chemoselective peptide chemical ligation reactions paved the way to such complex molecular architectures of considerable potential for protein therapeutics. To date, the most popular strategy to introduce amide bond surrogates in proteins relies on an elaborate combination of 1) solutionphase synthesis to provide a suitably protected pseudo-dipeptide, 2) solid-phase peptide synthesis (SPPS) to incorporate the modification in a peptide fragment, and 3) native chemical ligation (NCL) to yield a full-length backbone-engineered protein. A valuable alternative for the introduction of amide-bond mimics in proteins would be a peptidomimetic ligation strategy combining in a single step the formation of the amide surrogate, its incorporation in a peptide backbone, and ligation of fragments. Besides the pioneering study on thioester backbone-engineered proteins, only few examples have been reported, including a recent study concerning a ligation of thioacidand aziridine-terminated model peptides, giving a reduced form (Y[CH2NH2]) of an amide bond. To enlarge the palette of the synthetic protein chemist, we envisioned developing a new peptidomimetic ligation prototype that leads to bioactive backbone-modified proteins. Herein, we report for the first time the use of the Cu-mediated cycloaddition of azides and terminal alkynes (CuAAC) for the assembly of unprotected peptide fragments into a bioactive triazole-containing protein. |
| Databáze: | OpenAIRE |
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