Total chemical synthesis of lassomycin and lassomycin-amide.
Herein we report a practical synthetic route to the lasso peptide lassomycin () and C-terminal variant lassomycin-amide (). The biological evaluation of peptides and against Mycobacterium tuberculosis revealed that neither had any activity against this bacterium. This lack of biological activity has led us to propose that naturally occurring lassomycin may actually exhibit a standard lasso peptide threaded conformation rather than the previously reported unthreaded structure.
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. s.l.cobb@durham.ac.uk.
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S
Lear
St. George's University of London, London, SW17 0RE, UK.
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T
Munshi
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. s.l.cobb@durham.ac.uk.
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Hudson
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. s.l.cobb@durham.ac.uk.
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Hatton
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA. Clarissa_Sit@hms.harvard.edu.
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J
Clardy
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. s.l.cobb@durham.ac.uk.
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JA
Mosely
St. George's University of London, London, SW17 0RE, UK.
T J
TJ
Bull
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA. Clarissa_Sit@hms.harvard.edu.
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CS
Sit
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. s.l.cobb@durham.ac.uk.
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Cobb
D019732:Amide Synthases / Q000737:chemistry*; D000595:Amino Acid Sequence; D060326:Chemistry Techniques, Synthetic; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D011487:Protein Conformation
D010456:Peptides, Cyclic; C000595674:lassomycin; D019732:Amide Synthases