Design and Synthesis of Nucleoproline Amino Acids for the Straightforward Preparation of Chiral and Conformationally Constrained Nucleopeptides |
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Authors: | Konrad H Bleicher Helma Wennemers |
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Institution: | 1. Discovery Chemistry, PRCB, F. Hoffmann‐La Roche AG, Grenzacherstrasse 124, CH‐4070 Basel, (fax: +41?44?68?86965);2. Laboratorium für Organische Chemie, Departement für Chemie und Angewandte Biowissenschaften, ETH‐Zürich, H?nggerberg HCI, Wolfgang‐Pauli‐Strasse 10, CH‐8093 Zürich, (fax: +41?44?632?1223) |
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Abstract: | A straightforward synthesis of orthogonally protected nucleoproline (Nup) amino acids and their coupling to oligomers are described. A key step is the attachment of alkynylated nucleobases to Fmoc‐protected 4‐azidoproline (Fmoc‐Azp‐OH) by a Cu‐catalyzed 1,3‐dipolar cycloaddition (‘click reaction’). The developed protocol allows preparation of the nucleoprolines in scales of >30 g. Solid‐phase peptide synthesis proved to be straightforward with these Nup amino acids. The resulting oligonucleoproline peptides adopt defined helices, are very well H2O soluble, and show comparable cell‐penetrating properties as recently reported α‐nucleoalanine peptides. |
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Keywords: | Nucleopeptides ‘ Click chemistry’ Peptides Cycloadditions Copper catalysis Catalysis Proline derivatives |
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