Discovery of high affinity inhibitors of Leishmania donovani N-myristoyltransferase

Mark D. Rackham; Zhiyong Yu; James A. Brannigan; William P. Heal; Daniel Paape; K. Victoria Barker; Anthony J. Wilkinson; Deborah F. Smith; Robin J. Leatherbarrow; Edward W. Tate

doi:10.1039/c5md00241a

Discovery of high affinity inhibitors of Leishmania donovani N-myristoyltransferase

Mark D. Rackham, Zhiyong Yu, James A. Brannigan, William P. Heal, Daniel Paape, K. Victoria Barker, Anthony J. Wilkinson, Deborah F. Smith, Robin J. Leatherbarrow, Edward W. Tate^*

^*Corresponding author for this work

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

Abstract

N-Myristoyltransferase (NMT) is a potential drug target in Leishmania parasites. Scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for Leishmania donovani NMT; development led to high affinity inhibitors with excellent ligand efficiency. The binding mode was characterised by crystallography and provides a structural rationale for selectivity.

Original language	English
Pages (from-to)	1761-1766
Number of pages	6
Journal	MedChemComm
Volume	6
Issue number	10
DOIs	https://doi.org/10.1039/c5md00241a
Publication status	Published - 17 Aug 2015

Access to Document

10.1039/c5md00241a

Cite this

@article{f1ac8c79f9d841b2a4b61cf1d3aa9292,

title = "Discovery of high affinity inhibitors of Leishmania donovani N-myristoyltransferase",

abstract = "N-Myristoyltransferase (NMT) is a potential drug target in Leishmania parasites. Scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for Leishmania donovani NMT; development led to high affinity inhibitors with excellent ligand efficiency. The binding mode was characterised by crystallography and provides a structural rationale for selectivity.",

author = "Rackham, {Mark D.} and Zhiyong Yu and Brannigan, {James A.} and Heal, {William P.} and Daniel Paape and Barker, {K. Victoria} and Wilkinson, {Anthony J.} and Smith, {Deborah F.} and Leatherbarrow, {Robin J.} and Tate, {Edward W.}",

year = "2015",

month = aug,

day = "17",

doi = "10.1039/c5md00241a",

language = "English",

volume = "6",

pages = "1761--1766",

journal = "MedChemComm",

issn = "2040-2503",

publisher = "The Royal Society of Chemistry",

number = "10",

}

TY - JOUR

T1 - Discovery of high affinity inhibitors of Leishmania donovani N-myristoyltransferase

AU - Rackham, Mark D.

AU - Yu, Zhiyong

AU - Brannigan, James A.

AU - Heal, William P.

AU - Paape, Daniel

AU - Barker, K. Victoria

AU - Wilkinson, Anthony J.

AU - Smith, Deborah F.

AU - Leatherbarrow, Robin J.

AU - Tate, Edward W.

PY - 2015/8/17

Y1 - 2015/8/17

N2 - N-Myristoyltransferase (NMT) is a potential drug target in Leishmania parasites. Scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for Leishmania donovani NMT; development led to high affinity inhibitors with excellent ligand efficiency. The binding mode was characterised by crystallography and provides a structural rationale for selectivity.

AB - N-Myristoyltransferase (NMT) is a potential drug target in Leishmania parasites. Scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective for Leishmania donovani NMT; development led to high affinity inhibitors with excellent ligand efficiency. The binding mode was characterised by crystallography and provides a structural rationale for selectivity.

UR - http://www.scopus.com/inward/record.url?scp=84943797209&partnerID=8YFLogxK

U2 - 10.1039/c5md00241a

DO - 10.1039/c5md00241a

M3 - Article

AN - SCOPUS:84943797209

SN - 2040-2503

VL - 6

SP - 1761

EP - 1766

JO - MedChemComm

JF - MedChemComm

IS - 10

ER -

Discovery of high affinity inhibitors of Leishmania donovani N-myristoyltransferase

Abstract

Access to Document

Other files and links

Cite this