The synthesis of an array of stapled polyproline peptides

The purpose of this investigation was to determine if a short all hydrocarbon linker can be used to staple a polyproline chain and therein favouan alternative conformation to the typical type exhibited in an aqueous environment. An array of functionalised P(Pro)7 peptides were synthesised with olefin containing sidechains present at the 4C position on the 4th and 7th monomer units. Ruthenium-catalysed olefin metathesis was then used to form an all hydrocarbon i-i+3 linker between the two sidechains, effectively 'stapling' the peptide at the C-terminal. The conformation of the subsequent 'stapled' peptides was then investigated using, FT-IR and circular dichroism (CD), to determine the polyproline type I or type II character. The stapling of the peptides proved to alter the conformation from the typical PolPro2 character exhibited in an aqueous environment.