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Giant macrolactams based on ?-sheet peptides.

ABSTRACT: This paper reports the use of natural amino acids, the tripeptide ?-strand mimic Hao, and the ?-turn mimic ?-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 ?-sheet structures in aqueous solutions.

SUBMITTER: Cheng PN

PROVIDER: S-EPMC3088102 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Giant macrolactams based on β-sheet peptides.

Cheng Pin-Nan PN Nowick James S JS

The Journal of organic chemistry 20110415 9

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 pepti ...[more]

PMID: 21452877

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