1. On-resin microwave-assisted copper-catalyzed azide-alkyne cycloaddition of H1-relaxin B single chain 'stapled' analogues
- Author
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L. Pacini, Ilaria Capecchi, Anna Maria Papini, Annunziata D’Ercole, Paolo Rovero, Elisa Impresari, and Giuseppina Sabatino
- Subjects
chemistry.chemical_classification ,Relaxin ,Chemistry ,Organic Chemistry ,Biophysics ,Alkyne ,Single chain ,stapled peptides ,microwave-assisted click reaction ,Biochemistry ,Combinatorial chemistry ,Microwave assisted ,H1-relaxin B chain ,on-resin CuAAC ,Cycloaddition ,Biomaterials ,chemistry.chemical_compound ,Copper catalyzed ,Azide - Abstract
The development of conformationally constrained analogues of bioactive peptides is a relevant goal in peptide medicinal chemistry. Among the several classes of conformationally constrained peptides, the so-called stapled peptides, which bear a side-chain-to-side-chain bridge, are particularly interesting since they offer the possibility to stabilize specific conformational elements, such as a-helices or beta-turns. We describe an efficient and reproducible microwave-assisted strategy to prepare side-chain-to-side-chain clicked peptides, performing the copper-catalyzed azide-alkyne cycloaddition on solid phase, using as a model peptide a portion of the H1-relaxin B chain, which contains the binding cassette motif of this important bioactive peptide. All the relevant parameters, that is, resin, solvent, catalytic system, microwave energy and reaction time were optimized using a systematic one-factor-at-a-time (OFAT) approach. This method will be useful for the preparation of libraries of conformationally constrained relaxin analogues.
- Published
- 2020