Cargando…

Chirality: a key parameter in chemical probes

Many small molecule bioactive and marketed drugs are chiral. They are often synthesised from commercially available chiral building blocks. However, chirality is sometimes incorrectly assigned by manufacturers with consequences for the end user ranging from: experimental irreproducibility, wasted ti...

Descripción completa

Detalles Bibliográficos
Autores principales: McGown, Andrew, Nafie, Jordan, Otayfah, Mohammed, Hassell-Hart, Storm, Tizzard, Graham J., Coles, Simon J., Banks, Rebecca, Marsh, Graham P., Maple, Hannah J., Kostakis, George E., Proietti Silvestri, Ilaria, Colbon, Paul, Spencer, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549247/
https://www.ncbi.nlm.nih.gov/pubmed/37799583
http://dx.doi.org/10.1039/d3cb00082f
_version_ 1785115382141419520
author McGown, Andrew
Nafie, Jordan
Otayfah, Mohammed
Hassell-Hart, Storm
Tizzard, Graham J.
Coles, Simon J.
Banks, Rebecca
Marsh, Graham P.
Maple, Hannah J.
Kostakis, George E.
Proietti Silvestri, Ilaria
Colbon, Paul
Spencer, John
author_facet McGown, Andrew
Nafie, Jordan
Otayfah, Mohammed
Hassell-Hart, Storm
Tizzard, Graham J.
Coles, Simon J.
Banks, Rebecca
Marsh, Graham P.
Maple, Hannah J.
Kostakis, George E.
Proietti Silvestri, Ilaria
Colbon, Paul
Spencer, John
author_sort McGown, Andrew
collection PubMed
description Many small molecule bioactive and marketed drugs are chiral. They are often synthesised from commercially available chiral building blocks. However, chirality is sometimes incorrectly assigned by manufacturers with consequences for the end user ranging from: experimental irreproducibility, wasted time on synthesising the wrong product and reanalysis, to the added cost of purchasing the precursor and resynthesis of the correct stereoisomer. Further on, this could lead to loss of reputation, loss of funding, to safety and ethical concerns due to potential in vivo administration of the wrong form of a drug. It is our firm belief that more stringent control of chirality be provided by the supplier and, if needed, requested by the end user, to minimise the potential issues mentioned above. Certification of chirality would bring much needed confidence in chemical structure assignment and could be provided by a variety of techniques, from polarimetry, chiral HPLC, using known chiral standards, vibrational circular dichroism, and x-ray crystallography. A few case studies of our brushes with wrong chirality assignment are shown as well as some examples of what we believe to be good practice.
format Online
Article
Text
id pubmed-10549247
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher RSC
record_format MEDLINE/PubMed
spelling pubmed-105492472023-10-05 Chirality: a key parameter in chemical probes McGown, Andrew Nafie, Jordan Otayfah, Mohammed Hassell-Hart, Storm Tizzard, Graham J. Coles, Simon J. Banks, Rebecca Marsh, Graham P. Maple, Hannah J. Kostakis, George E. Proietti Silvestri, Ilaria Colbon, Paul Spencer, John RSC Chem Biol Chemistry Many small molecule bioactive and marketed drugs are chiral. They are often synthesised from commercially available chiral building blocks. However, chirality is sometimes incorrectly assigned by manufacturers with consequences for the end user ranging from: experimental irreproducibility, wasted time on synthesising the wrong product and reanalysis, to the added cost of purchasing the precursor and resynthesis of the correct stereoisomer. Further on, this could lead to loss of reputation, loss of funding, to safety and ethical concerns due to potential in vivo administration of the wrong form of a drug. It is our firm belief that more stringent control of chirality be provided by the supplier and, if needed, requested by the end user, to minimise the potential issues mentioned above. Certification of chirality would bring much needed confidence in chemical structure assignment and could be provided by a variety of techniques, from polarimetry, chiral HPLC, using known chiral standards, vibrational circular dichroism, and x-ray crystallography. A few case studies of our brushes with wrong chirality assignment are shown as well as some examples of what we believe to be good practice. RSC 2023-08-08 /pmc/articles/PMC10549247/ /pubmed/37799583 http://dx.doi.org/10.1039/d3cb00082f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
McGown, Andrew
Nafie, Jordan
Otayfah, Mohammed
Hassell-Hart, Storm
Tizzard, Graham J.
Coles, Simon J.
Banks, Rebecca
Marsh, Graham P.
Maple, Hannah J.
Kostakis, George E.
Proietti Silvestri, Ilaria
Colbon, Paul
Spencer, John
Chirality: a key parameter in chemical probes
title Chirality: a key parameter in chemical probes
title_full Chirality: a key parameter in chemical probes
title_fullStr Chirality: a key parameter in chemical probes
title_full_unstemmed Chirality: a key parameter in chemical probes
title_short Chirality: a key parameter in chemical probes
title_sort chirality: a key parameter in chemical probes
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10549247/
https://www.ncbi.nlm.nih.gov/pubmed/37799583
http://dx.doi.org/10.1039/d3cb00082f
work_keys_str_mv AT mcgownandrew chiralityakeyparameterinchemicalprobes
AT nafiejordan chiralityakeyparameterinchemicalprobes
AT otayfahmohammed chiralityakeyparameterinchemicalprobes
AT hassellhartstorm chiralityakeyparameterinchemicalprobes
AT tizzardgrahamj chiralityakeyparameterinchemicalprobes
AT colessimonj chiralityakeyparameterinchemicalprobes
AT banksrebecca chiralityakeyparameterinchemicalprobes
AT marshgrahamp chiralityakeyparameterinchemicalprobes
AT maplehannahj chiralityakeyparameterinchemicalprobes
AT kostakisgeorgee chiralityakeyparameterinchemicalprobes
AT proiettisilvestriilaria chiralityakeyparameterinchemicalprobes
AT colbonpaul chiralityakeyparameterinchemicalprobes
AT spencerjohn chiralityakeyparameterinchemicalprobes