Introduction of all-hydrocarbon i,i+3 staples into alpha-helices via ring-closing olefin metathesis.
The introduction of all-hydrocarbon i,i+3 staples into alpha-helical peptide scaffolds via ring-closing olefin metathesis (RCM) between two alpha-methyl,alpha-pentenylglycine residues incorporated at i and i+3 positions, which lie on the same face of the helix, has been investigated. The reactions were found to be highly dependent upon the side-chain stereochemistry of the amino acids undergoing RCM. The i,i+3 stapling system established here provides a potentially useful alternative to the well-established i,i+4 stapling system now in widespread use.
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA.
Young-Woo
YW
Kim
Peter S
PS
Kutchukian
Gregory L
GL
Verdine
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D003500:Cyclization; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D013997:Time Factors
D000475:Alkenes; D000596:Amino Acids; D010455:Peptides