Incorporation of conformationally constrained beta-amino acids into peptides.
The use of norbornene units to induce the formation of beta-sheet and beta-turn type structures in peptides is discussed. The norbornene unit is readily prepared by a desymmetrization reaction and is easily incorporated into a peptide chain. Depending upon the exact nature of the norbornene unit, it is possible to form structures which resemble parallel beta-sheets, antiparallel beta-sheets or beta-turns. Similar peptide analogues incorporating a cis-2-amino-cyclopropane carboxylic acid unit can also be prepared. As an illustration of the application of this chemistry, a short, asymmetric synthesis of conformationally constrained metalloprotease inhibitors is presented.
North
M
M
Department of Chemistry, King's College, Strand, London, UK. michael.north@Kcl.ac.uk
D000596:Amino Acids / Q000737:chemistry*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry; D006860:Hydrogen Bonding; D009636:Norbornanes / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000596:Amino Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D003521:Cyclopropanes; D009636:Norbornanes; D010455:Peptides; C030797:cyclopropane