A new method for the pre-activation cyclization of a long peptide is described. The approach involves the formation of a pre-activated succinimidyl ester species in advance of amidation, which completely eliminates the potentially troublesome amine end-capping side reaction. The cyclization reactions proceed with high efficiency and fast reaction kinetics for the long peptide with 25 residues. The exploration and large-scale preparation of synthetic cyclic peptides should become more accessible and feasible with this approach. This method has a potential to be further applied for the synthesis of much longer and more complex cyclic peptides.
Bibliographical noteFunding Information:
This work was supported by grants from the National Research Foundation (NRF) of Korea ( 2014R1A2A1A11050359 , 2012R1A1A2006453 , 2009-0083522 , and 2014-11-1272 ), the Agency for Defense Development through Chemical and Biological Defense Research Center ( 2014-0787-009 ), Civil-Military Technology Cooperation Program , and Yonsei University Future-leading Research Initiative .
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry