Solid-Phase Synthesis of Wollamide Cyclohexapeptide Analogs

Methods Mol Biol. 2020:2103:175-187. doi: 10.1007/978-1-0716-0227-0_11.

Abstract

Mycobacterium tuberculosis (Mtb) is a bacterial pathogen that causes a potentially serious infectious disease called tuberculosis (TB). Cyclohexapeptide wollamides A and B were recently isolated from Streptomyces nov. sp. (MST-115088) and subsequently reported to show excellent in vitro antituberculosis activity with minimum inhibitory concentration (MIC) of 1.56 μg/mL against Mtb (H37Rv) and favorable selectivity profile. This chapter describes the detailed synthesis of antitubercular wollamide analogs using solid-phase synthesis of linear hexapeptide precursors, followed by solution-phase HBTU-mediated macrocyclization and global side chain deprotection.

Keywords: Antituberculosis; Cyclohexapeptide; Macrocyclization; Mycobacterium tuberculosis; Solid-phase peptide synthesis; Wollamide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / isolation & purification
  • Antitubercular Agents / pharmacology
  • Cyclization
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification
  • Peptides, Cyclic / pharmacology
  • Solid-Phase Synthesis Techniques / methods*

Substances

  • Antitubercular Agents
  • Peptides, Cyclic