Total chemical synthesis of lassomycin and lassomycin-amide

S. Lear; T. Munshi; A. S. Hudson; C. Hatton; J. Clardy; J. A. Mosely; T. J. Bull; C. S. Sit; S. L. Cobb

doi:10.1039/c6ob00631k

Total chemical synthesis of lassomycin and lassomycin-amide

S. Lear, T. Munshi, A. S. Hudson, C. Hatton, J. Clardy, J. A. Mosely, T. J. Bull, C. S. Sit, S. L. Cobb

National Horizons Centre

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

Herein we report a practical synthetic route to the lasso peptide lassomycin (1) and C-terminal variant lassomycin-amide (2). The biological evaluation of peptides 1 and 2 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.

Original language	English
Pages (from-to)	4534-4541
Number of pages	8
Journal	Organic and Biomolecular Chemistry
Volume	14
Issue number	19
DOIs	https://doi.org/10.1039/c6ob00631k
Publication status	Published - 12 Apr 2016

Bibliographical note

Funding Information:
We gratefully acknowledge financial support from the EPSRC (Durham University EPSRC DTG, SL). CSS was funded by an Alberta Innovates Health Solutions Fellowship and a Banting Postdoctoral Fellowship. In addition, we thank Dr Juan A. Aguilar Malavia (Durham University) for the collection and processing of 2D NMR data.

Publisher Copyright:
© The Royal Society of Chemistry 2016.

Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.

Access to Document

10.1039/c6ob00631k

Cite this

@article{08d5e1ed2c5e42c38dcec0d6d6924e23,

title = "Total chemical synthesis of lassomycin and lassomycin-amide",

abstract = "Herein we report a practical synthetic route to the lasso peptide lassomycin (1) and C-terminal variant lassomycin-amide (2). The biological evaluation of peptides 1 and 2 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.",

author = "S. Lear and T. Munshi and Hudson, {A. S.} and C. Hatton and J. Clardy and Mosely, {J. A.} and Bull, {T. J.} and Sit, {C. S.} and Cobb, {S. L.}",

note = "Funding Information: We gratefully acknowledge financial support from the EPSRC (Durham University EPSRC DTG, SL). CSS was funded by an Alberta Innovates Health Solutions Fellowship and a Banting Postdoctoral Fellowship. In addition, we thank Dr Juan A. Aguilar Malavia (Durham University) for the collection and processing of 2D NMR data. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2016. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.",

year = "2016",

month = apr,

day = "12",

doi = "10.1039/c6ob00631k",

language = "English",

volume = "14",

pages = "4534--4541",

journal = "Organic and Biomolecular Chemistry",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

number = "19",

}

TY - JOUR

T1 - Total chemical synthesis of lassomycin and lassomycin-amide

AU - Lear, S.

AU - Munshi, T.

AU - Hudson, A. S.

AU - Hatton, C.

AU - Clardy, J.

AU - Mosely, J. A.

AU - Bull, T. J.

AU - Sit, C. S.

AU - Cobb, S. L.

N1 - Funding Information: We gratefully acknowledge financial support from the EPSRC (Durham University EPSRC DTG, SL). CSS was funded by an Alberta Innovates Health Solutions Fellowship and a Banting Postdoctoral Fellowship. In addition, we thank Dr Juan A. Aguilar Malavia (Durham University) for the collection and processing of 2D NMR data. Publisher Copyright: © The Royal Society of Chemistry 2016. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.

PY - 2016/4/12

Y1 - 2016/4/12

N2 - Herein we report a practical synthetic route to the lasso peptide lassomycin (1) and C-terminal variant lassomycin-amide (2). The biological evaluation of peptides 1 and 2 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.

AB - Herein we report a practical synthetic route to the lasso peptide lassomycin (1) and C-terminal variant lassomycin-amide (2). The biological evaluation of peptides 1 and 2 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.

UR - http://www.scopus.com/inward/record.url?scp=84970971198&partnerID=8YFLogxK

U2 - 10.1039/c6ob00631k

DO - 10.1039/c6ob00631k

M3 - Article

C2 - 27101411

AN - SCOPUS:84970971198

SN - 1477-0520

VL - 14

SP - 4534

EP - 4541

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 19

ER -

Total chemical synthesis of lassomycin and lassomycin-amide

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this