A Tandem In Situ Peptide Cyclization through Trifluoroacetic Acid Cleavage |
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| Authors: | Dr Koushik Chandra Dr Tapta Kanchan Roy Dr Deborah E Shalev Prof Abraham Loyter Prof Chaim Gilon Prof R Benny Gerber Prof Assaf Friedler |
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| Institution: | 1. Institute of Chemistry, Edmond J. Safra campus The Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904 (Israel) http://chem.ch.huji.ac.il/～assaf;2. The Wolfson Centre for Applied Structural Biology, The Hebrew University of Jerusalem (Israel);3. Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem (Israel);4. The Fritz Haber Centre, The Hebrew University of Jerusalem (Israel);5. Department of Chemistry, University of Helsinki, P.O. Box 55, 00014 Helsinki (Finland);6. University of California, Irvine, CA 92697 (USA) |
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| Abstract: | We present a new approach for peptide cyclization during solid phase synthesis under highly acidic conditions. Our approach involves simultaneous in situ deprotection, cyclization and trifluoroacetic acid (TFA) cleavage of the peptide, which is achieved by forming an amide bond between a lysine side chain and a succinic acid linker at the peptide N‐terminus. The reaction proceeds via a highly active succinimide intermediate, which was isolated and characterized. The structure of a model cyclic peptide was solved by NMR spectroscopy. Theoretical calculations support the proposed mechanism of cyclization. Our new methodology is applicable for the formation of macrocycles in solid‐phase synthesis of peptides and organic molecules. |
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| Keywords: | cyclic peptides cyclization peptide NMR spectroscopy peptide synthesis peptides |
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