Oral Presentation 11th Australian Peptide Conference 2015

Peptide transition metal complexes in catalysis and proteolysis (#20)

Morten Meldal 1 , Carlos Aydillo , Martin Wolfram , Ahmed Embaby , David B Nygård , Christian A Christensen , Kasper W Leomhard , Jakob F Jensen
  1. University of Copenhagen, Copenhagen, DK, Denmark

A variety of different approaches to solid phase synthesis of peptide ligands incorporating carbenes, phosphines and nitrogen heterocycles have been developed.(1,2) For peptide carbene ligands the carbene precursors were incorporated as  Fmoc-dipeptide mimicking building blocks in conventional synthesis or they were synthesized with a functionality allowing CuAAC- and thiol-ene click chemistry or simple amide bond formation for combinatorial post modification of libraries. The phosphines were introduces by post peptide assembly by modification of secondary amines obtained through reductive amination. Bipyridine was introduced as an Fmoc-building block and phenantroline by reductive macrocyclization of a bis-aldehyde to selectively deprotected peptide amines.   The ligands were used in complexation of transition metals such as Pd, Ir, Co, Cu Fe and Zn. Metal complexation was verified by HR-MS and these "organozyme" catalysts were used in a variety of catalytic reactions to demonstrate high turnover and selectivity. Most importantly it was demonstrated that these amazing transition metal complexes are active and quite selective as “organozymes” acting as proteases to selectively cleave certain peptide bonds in FRET substrates. The potential of peptides in selective proteolysis will be discussed.

  1. Christensen, C. A., Meldal, M. (2004). Efficient Solid-Phase Synthesis of Peptide Based Phosphine Ligands: Towards Combinatorial Libraries of Selective Transition Metal Catalysts. Chemistry - A European Journal, 11, 4121-4131.
  2. Worm-Leonhard, K., Meldal, M. (2008). Green catalysts: Solid-phase peptide carbene ligands in aqueous transition metal catalysis. European Journal of Organic Chemistry, 2008, 5244-5253.