Dihydroxyphenylglycine

Dihydroxyphenylglycine

Names
IUPAC name (S)-2-amino-2-(3,5-dihydroxyphenyl)acetic acid
Other names 3,5-dihydroxyphenylglycine, DHPG, S-DHPG
Identifiers
CAS Number	162870-29-3 Y
3D model (JSmol)	Interactive image
ChemSpider	11377133 Y
MeSH	3,5-dihydroxyphenylglycine
PubChem CID	443586
UNII	CF5G2G268A Y
InChI InChI=1S/C8H9NO4/c10-6-3-1-2-5(8(6)13)9-4-7(11)12/h1-3,9-10,13H,4H2,(H,11,12) Y Key: RCPPFACRJDEDFY-UHFFFAOYSA-N Y InChI=1/C8H9NO4/c10-6-3-1-2-5(8(6)13)9-4-7(11)12/h1-3,9-10,13H,4H2,(H,11,12) Key: RCPPFACRJDEDFY-UHFFFAOYAU
SMILES C1=CC(=C(C=C1[C@@H](C(=O)O)N)O)O
Properties
Chemical formula	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). Y verify (what is YN ?) Infobox references

(S)-3,5-Dihydroxyphenylglycine or DHPG is a potent agonist of group I metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5.

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.

Biosynthesis

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.

References