Willardiine

Willardiine

Flowers of Mariosousa willardiana
Names
IUPAC name
3-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-L-alanine
Systematic IUPAC name
(2S)-2-Amino-3-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanoic acid
Other names
  • 3-(Uracil-1-yl)-L-alanine
  • 3-(1-Uracyl)-L-alanine
Identifiers
3D model (JSmol)
20710
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
MeSH Willardiine
  • InChI=1S/C7H9N3O4/c8-4(6(12)13)3-10-2-1-5(11)9-7(10)14/h1-2,4H,3,8H2,(H,12,13)(H,9,11,14)/t4-/m0/s1
    Key: FACUYWPMDKTVFU-BYPYZUCNSA-N
  • C1=CN(C(=O)NC1=O)C[C@@H](C(=O)O)N
Properties
C7H9N3O4
Molar mass 199.166 g·mol−1
log P −4.4
Acidity (pKa) 2.97
Basicity (pKb) 9.76
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Willardiine (correctly spelled with two successive i's) or (S)-1-(2-amino-2-carboxyethyl)pyrimidine-2,4-dione is a chemical compound that occurs naturally in the seeds of Mariosousa willardiana and Acacia sensu lato.[1] The seedlings of these plants contain enzymes capable of complex chemical substitutions that result in the formation of free amino acids (See: #Synthesis). Willardiine is frequently studied for its function in higher level plants. Additionally, many derivates of willardiine are researched for their potential in pharmaceutical development.[1] Willardiine was first discovered in 1959 by R. Gmelin, when he isolated several free, non-protein amino acids from Acacia willardiana (another name for Mariosousa willardiana) when he was studying how these families of plants synthesize uracilyalanines.[2] A related compound, Isowillardiine, was concurrently isolated by a different group, and it was discovered that the two compounds had different structural and functional properties.[3] Subsequent research on willardiine has focused on the functional significance of different substitutions at the nitrogen group and the development of analogs of willardiine with different pharmacokinetic properties. In general, Willardiine is the one of the first compounds studied in which slight changes to molecular structure result in compounds with significantly different pharmacokinetic properties.[4]

Willardiine is a partial agonist of Ionotropic glutamate receptors. These receptors are found at excitatory synapses and bind glutamate (the major excitatory neurotransmitter) and structurally similar ligands, such as willardiine. Receptor activation leads to influx of positive ions into the neuron, resulting in neural depolarization (See: #Structure and Activity). Willardiine specifically agonizes non-NMDA glutamate receptors: AMPA and kainate receptors.[3]

Willardiine analogs have been developed that have different binding affinities for the AMPA and kainate receptors. These analogs have been used to study the structure of these receptors, as well as the functional significance of receptor activation in different brain regions.[4] While willardiine and its analogs have not been explicitly studied as therapeutics, there are a variety of neurological disorders characterized by alterations in glutamate signaling, and ligands for AMPA and kainate receptors are often studied as potential therapeutics.[5]

  1. ^ a b Viso, Alma; Fernández de la Pradilla, Roberto; García, Ana; Flores, Aida (August 2005). "α,β-Diamino Acids: Biological Significance and Synthetic Approaches". Chemical Reviews. 105 (8): 3167–3196. doi:10.1021/cr0406561. hdl:10261/343620. ISSN 0009-2665. PMID 16092828.
  2. ^ Kjær, Anders; Knudsen, Allan; Larsen, P. Olesen (1961). "Amino acid studies. Part IV. Structure and synthesis of the plant amino acid willardiine [3-(1-uracyl)-L-alanine]". Acta Chemica Scandinavica. 15: 1193–1195. doi:10.3891/acta.chem.scand.15-1193. ISSN 0904-213X.
  3. ^ a b Traynelis, Stephen F.; Wollmuth, Lonnie P.; McBain, Chris J.; Menniti, Frank S.; Vance, Katie M.; Ogden, Kevin K.; Hansen, Kasper B.; Yuan, Hongjie; Myers, Scott J.; Dingledine, Ray (September 2010). Sibley, David (ed.). "Glutamate Receptor Ion Channels: Structure, Regulation, and Function". Pharmacological Reviews. 62 (3): 405–496. doi:10.1124/pr.109.002451. ISSN 0031-6997. PMC 2964903. PMID 20716669.
  4. ^ a b Bunch, Lennart; Krogsgaard-Larsen, Povl (2009). "Subtype selective kainic acid receptor agonists: Discovery and approaches to rational design". Medicinal Research Reviews. 29 (1): 3–28. doi:10.1002/med.20133. ISSN 1098-1128. PMID 18623169. S2CID 11112717.
  5. ^ Cite error: The named reference :17 was invoked but never defined (see the help page).