title: Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis.
abstract: This protocol provides a detailed procedure for the preparation of stapled α-helical peptides, which have proven their potential as useful molecular probes and as next-generation therapeutics. Two crucial features of this protocol are (i) the construction of peptide substrates containing hindered α-methyl, α-alkenyl amino acids and (ii) the ring-closing olefin metathesis (RCM) of the resulting resin-bound peptide substrates. The stapling systems described in this protocol, namely bridging one or two turns of an α-helix, are highly adaptable to most peptide sequences, resulting in favorable RCM kinetics, helix stabilization and promotion of cellular uptake.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Tom N
authors.initials: TN
authors.lastname: Grossmann
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Verdine
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000595:Amino Acid Sequence; D057005:Bioengineering / Q000379:methods*; D006838:Hydrocarbons / Q000737:chemistry*; D007700:Kinetics; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D055550:Protein Stability; D017433:Protein Structure, Secondary
chemical_list: D000475:Alkenes; D006838:Hydrocarbons; D015335:Molecular Probes; D010455:Peptides