(S)-3,5-Dihydroxyphenylglycine or DHPG is a potent agonist of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5.
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IUPAC name
(S)-2-amino-2-(3,5-dihydroxyphenyl)acetic acid
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Other names
3,5-dihydroxyphenylglycine, DHPG, S-DHPG
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3D model (JSmol)
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MeSH | 3,5-dihydroxyphenylglycine |
PubChem CID
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Properties | |
C8H9NO4 | |
Molar mass | 183.05 g mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references
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DHPG was the first agonist shown to be selective for group I mGluRs.[1] Agonist activity is found in only the (S)-isomer, and (S)-DHPG may be a partial agonist of group I mGluRs.[1]
(S)-DHPG has been investigated for therapeutic effects in the treatment of neuronal injury (such as those associated with ischemia or hypoxia), cognitive enhancement, and Alzheimer's disease.[1]
3,5-Dihydroxyphenylglycine can be isolated from the latex of Euphorbia helioscopia.[2]
DHGP is also found in vancomycin and related glycopeptides. Although the (S) stereoisomer is synthesized by the DpgA-D enzymes,[3] it is the (R) stereoisomer that is used in vancomycin and other related compounds. DHPG is enzymatically derived from the polyketide synthase pathway.
When synthesized in bacteria, DHPG requires 5 enzymes, DpgA-D and 4-hydroxyphenylglycine transferase (Pgat), in order to be synthesized.[4] DpgA is a type III polyketide synthase and initiates the synthesis by condensing acetyl-CoA with three molecules of malonyl-CoA. The tetra-carbonyl compound then cyclizes to form a C8 intermediate. DpgB/D then dehydrates the intermediate using enolate chemistry to promote the loss of water. DpgB/D isomerizes the product to aromatize the ring.
DpgC oxidizes the aromatic intermediate at the benzylic carbon using oxygen to an alpha-keto compound. DpgC performs this oxidation in absence of any iron, heme, flavin, or pterin cofactors. Chen et al suggest the following reaction mechanism to explain the reactivity of DpgC.[5] This mechanism is supported by findings reported in Widboom et al in 2007.[6] Finally, the molecule is transaminated by 4-hydroxyphenylglycine transferase using tyrosine to become DHPG.
4-Hydroxyphenylglycine transferase synthesizes the (S) stereoisomer of DHPG, however, an epimerase switches the stereocenter to the (R) configuration after DHPG is incorporated into the vancomycin non-ribosomal polypeptide.