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Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives

[Image: see text] Menaquinones (MKs) contain both a redox active quinone moiety and a hydrophobic repeating isoprenyl side chain of varying lengths and degrees of saturation. This characteristic structure allows MKs to play a key role in the respiratory electron transport system of some prokaryotes...

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Autores principales: Koehn, Jordan T., Crick, Dean C., Crans, Debbie C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643618/
https://www.ncbi.nlm.nih.gov/pubmed/31458155
http://dx.doi.org/10.1021/acsomega.8b02620
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author Koehn, Jordan T.
Crick, Dean C.
Crans, Debbie C.
author_facet Koehn, Jordan T.
Crick, Dean C.
Crans, Debbie C.
author_sort Koehn, Jordan T.
collection PubMed
description [Image: see text] Menaquinones (MKs) contain both a redox active quinone moiety and a hydrophobic repeating isoprenyl side chain of varying lengths and degrees of saturation. This characteristic structure allows MKs to play a key role in the respiratory electron transport system of some prokaryotes by shuttling electrons and protons between membrane-bound protein complexes, which act as electron acceptors and donors. Hydrophobic MK molecules with partially and fully saturated isoprenyl side chains are found in a wide range of eubacteria and archaea, and the structural variations of the MK analogues are evolutionarily conserved but poorly understood. For example, Mycobacterium tuberculosis, the causative agent of tuberculosis, uses predominantly MK-9(II-H(2)) (saturated at the second isoprene unit) as its electron carrier and depends on the synthesis of MK-9(II-H(2)) for survival in host macrophages. Thus, MKs with partially saturated isoprenyl side chains may represent a novel virulence factor. Naturally occurring longer MKs are very hydrophobic, whereas MK analogues that have a truncated (i.e., one to three isoprenes) isoprenyl side chain are less hydrophobic. This improves their solubility in aqueous solutions, allowing rigorous study of their structure and biological activity. We present the synthesis and characterization of two partially saturated MK analogues, MK-2(II-H(2)) and MK-3(II-H(2)), and two novel fully saturated MK derivatives, MK-2(I,II-H(4)) and MK-3(I,II,III-H(6)).
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spelling pubmed-66436182019-08-27 Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives Koehn, Jordan T. Crick, Dean C. Crans, Debbie C. ACS Omega [Image: see text] Menaquinones (MKs) contain both a redox active quinone moiety and a hydrophobic repeating isoprenyl side chain of varying lengths and degrees of saturation. This characteristic structure allows MKs to play a key role in the respiratory electron transport system of some prokaryotes by shuttling electrons and protons between membrane-bound protein complexes, which act as electron acceptors and donors. Hydrophobic MK molecules with partially and fully saturated isoprenyl side chains are found in a wide range of eubacteria and archaea, and the structural variations of the MK analogues are evolutionarily conserved but poorly understood. For example, Mycobacterium tuberculosis, the causative agent of tuberculosis, uses predominantly MK-9(II-H(2)) (saturated at the second isoprene unit) as its electron carrier and depends on the synthesis of MK-9(II-H(2)) for survival in host macrophages. Thus, MKs with partially saturated isoprenyl side chains may represent a novel virulence factor. Naturally occurring longer MKs are very hydrophobic, whereas MK analogues that have a truncated (i.e., one to three isoprenes) isoprenyl side chain are less hydrophobic. This improves their solubility in aqueous solutions, allowing rigorous study of their structure and biological activity. We present the synthesis and characterization of two partially saturated MK analogues, MK-2(II-H(2)) and MK-3(II-H(2)), and two novel fully saturated MK derivatives, MK-2(I,II-H(4)) and MK-3(I,II,III-H(6)). American Chemical Society 2018-11-05 /pmc/articles/PMC6643618/ /pubmed/31458155 http://dx.doi.org/10.1021/acsomega.8b02620 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Koehn, Jordan T.
Crick, Dean C.
Crans, Debbie C.
Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
title Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
title_full Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
title_fullStr Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
title_full_unstemmed Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
title_short Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives
title_sort synthesis and characterization of partially and fully saturated menaquinone derivatives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643618/
https://www.ncbi.nlm.nih.gov/pubmed/31458155
http://dx.doi.org/10.1021/acsomega.8b02620
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