Synthesis of small mechanically-interlocked peptides: Application to the total synthesis of Microcin J25 (MccJ25)

ORGN 381

Andrew Richard Thomson, drew_r_thomson@hotmail.com1, David A. Leigh, David.Leigh@ed.ac.uk2, and Vincent Aucagne2. (1) School of Chemistry, Edinburgh University, The Kings Buildings, West Mains Road, Edinburgh, EH9 3JJ, United Kingdom, (2) School of Chemistry, University of Edinburgh, The King's Buildings, West Mains Road, EH9 3JJ, Edinburgh, United Kingdom
Studies on naturally occurring interlocked peptides have shown them to have many intriguing properties, but little specific data exists on the effect of kinetically stable entanglements on peptide and protein structure, function or folding. There is as yet no synthetic methodology for producing interlocked peptide or protein architectures. MccJ25 is a small ribosomally-synthesized defense antibiotic peptide secreted by Enterobacteriaceae. The structure of MccJ25 has been described as “lassoed”: at one end of the 21-amino-acid peptide is a ring formed by an amide linkage between the N-terminus and the side chain of Glu8. The C-terminus loops back and threads through the cyclic part. ‘Dethreading' of this rotaxane-like secondary structure is blocked by Tyr20 and Phe19 on either side of the macrocycle. Here we describe the first synthetic route to interlocked peptide architectures and its application to the total synthesis of Microcin J25.
 

Proteins, Peptides, Amino Acids, and Enzymes
8:00 AM-11:40 AM, Tuesday, 15 March 2005 Convention Center -- Room 9, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005