Comparative α‐Helicity of Cyclic Pentapeptides in Water |
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| Authors: | Dr. Aline D. de Araujo Dr. Huy N. Hoang Dr. W. Mei Kok Dr. Frederik Diness Dr. Praveer Gupta Dr. Timothy A. Hill Dr. Russell W. Driver Dr. David A. Price Dr. Spiros Liras Prof. David P. Fairlie |
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| Affiliation: | 1. Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072 (Australia);2. Present address: Center for Evolutionary Chemical Biology, Department of Chemistry, University of Copenhagen, Copenhagen (Denmark);3. Present address: Life Sciences Incubator, IKP Knowledge Park, Hyderabad (India);4. World Wide Medicinal Chemistry, CVMED, Pfizer, Cambridge, MA (USA) |
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| Abstract: | Helix‐constrained polypeptides have attracted great interest for modulating protein–protein interactions (PPI). It is not known which are the most effective helix‐inducing strategies for designing PPI agonists/antagonists. Cyclization linkers (X1–X5) were compared here, using circular dichroism and 2D NMR spectroscopy, for α‐helix induction in simple model pentapeptides, Ac‐cyclo(1,5)‐[X1‐Ala‐Ala‐Ala‐X5]‐NH2, in water. In this very stringent test of helix induction, a Lys1→Asp5 lactam linker conferred greatest α‐helicity, hydrocarbon and triazole linkers induced a mix of α‐ and 310‐helicity, while thio‐ and dithioether linkers produced less helicity. The lactam‐linked cyclic pentapeptide was also the most effective α‐helix nucleator attached to a 13‐residue model peptide. |
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| Keywords: | α ‐helix circular dichroism cyclic peptides helix induction NMR structure |
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