title: Giant macrolactams based on β-sheet peptides.
abstract: This paper reports the use of natural amino acids, the tripeptide β-strand mimic Hao, and the β-turn mimic δ-linked ornithine to generate water-soluble 54-, 78-, and 102-membered-ring macrolactams. These giant macrocycles were efficiently prepared by synthesis of the corresponding protected linear peptides, followed by solution-phase cyclization and deprotection. The protected linear peptide precursors were synthesized on 2-chlorotrityl chloride resin by conventional Fmoc-based solid-phase peptide synthesis. Macrocyclization was typically performed using HCTU and N,N-diisopropylethylamine in DMF at ca. 0.5 mM concentration. The macrocycles were isolated in 13-45% overall yield after HPLC purification and lyophilization. 1D, 2D TOCSY, and 2D ROESY (1)H NMR studies of the 54- and 78-membered-ring macrolactams establish that these compounds fold to form β-sheet structures in aqueous solutions.
authors: Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025, USA.
authors: Pin-Nan
authors: PN
authors: Cheng
authors: James S
authors: JS
authors: Nowick
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry; D015195:Drug Design; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009952:Ornithine / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D024322:Amino Acids, Aromatic; D047029:Lactams, Macrocyclic; D010455:Peptides; C482441:alpha-(3-hydrazinocarbonyl-4-methoxyanilino)-alpha-oxoacetic acid; D014867:Water; D009952:Ornithine