title: Cyclooligomerization of a helix-bearing template into macrocycles bearing multiple helices.
abstract: Cyclooligomerization was investigated for separating and spatially arranging helical peptides as discontinuous surfaces. Tetrapeptide H-[Ile-Ser-Lys(Ox)]-OH, containing a turn-inducing oxazole constraint, was connected through its lysine side chain via a beta-alanine linker to the C-terminus of a two-turn helical nonapeptide Ac-(cyclo-4,8)-LRL [KARAD](Aib). The resulting helix-appended template was self-condensed and cyclized to a library of macrocycles ( n = 2-6) containing multiple (2-6) helices. An NMR structure shows retention of alpha helicity in the cyclotrimer ( n = 3).
authors.affiliation: Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane QLD 4072, Australia.
authors.forename: Renée L
authors.initials: RL
authors.lastname: Beyer
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
mesh_terms: D003500:Cyclization; D008239:Lysine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D017434:Protein Structure, Tertiary; D015091:beta-Alanine / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D010080:Oxazoles; D010456:Peptides, Cyclic; D015091:beta-Alanine; D008239:Lysine