Nature Protocols 2011-06-01

Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis.

Young-Woo Kim, Tom N Grossmann, Gregory L Verdine

Index: Nat. Protoc. 6(6) , 761-71, (2011)

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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.