You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2009-07-25 00:10:07 UTC
Update Date2017-12-07 02:38:40 UTC
HMDB IDHMDB0012933
Secondary Accession Numbers
  • HMDB12933
Metabolite Identification
Common NameDynorphin A 1-8
DescriptionDynorphin A (1-8) is a fraction of Dynorphin A with only Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile peptide chain. Dynorphin A is an endogenous opioid peptide that produces non-opioid receptor-mediated neural excitation.Dynorphin induces calcium influx via voltage-sensitive calcium channels in sensory neurons by activating bradykinin receptors. This action of dynorphin at bradykinin receptors is distinct from the primary signaling pathway activated by bradykinin and underlies the hyperalgesia produced by pharmacological administration of dynorphin by the spinal route in rats and mice. Blockade of spinal B1 or B2 receptor also reverses persistent neuropathic pain but only when there is sustained elevation of endogenous spinal dynorphin, which is required for maintenance of neuropathic pain. These data reveal a mechanism for endogenous dynorphin to promote pain through its agonist action at bradykinin receptors and suggest new avenues for therapeutic intervention. Dynorphin A is a form of dynorphin.Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and a/b-neo-endorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of "big dynorphin."This 32-amino acid molecule consists of both dynorphin A and dynorphin B.Dynorphin A, dynorphin B, and big dynorphin all contain a high proportion of basic amino acid residues, in particular lysine and arginine (29.4%, 23.1%, and 31.2% basic residues, respectively), as well as many hydrophobic residues (41.2%, 30.8%, and 34.4% hydrophobic residues, respectively). Although dynorphins are found widely distributed in the CNS, they have the highest concentrations in the hypothalamus, medulla, pons, midbrain, and spinal cord. Dynorphins are stored in large (80-120 nm diameter) dense-core vesicles that are considerably larger than vesicles storing neurotransmitters. These large dense-core vesicles differ from small synaptic vesicles in that a more intense and prolonged stimulus is needed to cause the large vesicles to release their contents into the synaptic cleft. Dense-core vesicle storage is characteristic of opioid peptides storage. The first clues to the functionality of dynorphins came from Goldstein et al. in their work with opioid peptides. The group discovered an endogenous opioid peptide in the porcine pituitary that proved difficult to isolate. By sequencing the first 13 amino acids of the peptide, they created a synthetic version of the peptide with a similar potency to the natural peptide. Goldstein et al. applied the synthetic peptide to the guinea ileum longitudinal muscle and found it to be an extraordinarily potent opioid peptide. The peptide was called dynorphin (from the Greek dynamis=power) to describe its potency. Dynorphins exert their effects primarily through the κ-opioid receptor (KOR), a G-protein-coupled receptor. Two subtypes of KORs have been identified: K1 and K2. Although KOR is the primary receptor for all dynorphins, the peptides do have some affinity for the μ-opioid receptor (MOR), d-opioid receptor (DOR), N-methyl-D-aspartic acid (NMDA)-type glutamate receptor. Different dynorphins show different receptor selectivities and potencies at receptors. Big dynorphin and dynorphin A have the same selectivity for human KOR, but dynorphin A is more selective for KOR over MOR and DOR than is big dynorphin. Big dynorphin is more potent at KORs than is dynorphin A. Both big dynorphin and dynorphin A are more potent and more selective than dynorphin B (Wikipedia).
Structure
Thumb
Synonyms
ValueSource
Dynorphin a (1-8)HMDB
Dynorphin a fragment 1-8HMDB
Tyr-gly-gly-phe-leu-arg-arg-ileHMDB
Chemical FormulaC46H72N14O10
Average Molecular Weight981.1517
Monoisotopic Molecular Weight980.555584594
IUPAC Name(2S,3S)-2-[(2R)-2-[(2R)-2-{2-[(2R)-2-(2-{2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]acetamido}acetamido)-3-phenylpropanamido]-4-methylpentanamido}-5-carbamimidamidopentanamido]-5-carbamimidamidopentanamido]-3-methylpentanoic acid
Traditional Name(2S,3S)-2-[(2R)-2-[(2R)-2-{2-[(2R)-2-(2-{2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]acetamido}acetamido)-3-phenylpropanamido]-4-methylpentanamido}-5-carbamimidamidopentanamido]-5-carbamimidamidopentanamido]-3-methylpentanoic acid
CAS Registry Number75790-53-3
SMILES
CC[C@H](C)[C@H](NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=O)C(CC(C)C)NC(=O)[C@@H](CC1=CC=CC=C1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1)C(O)=O
InChI Identifier
InChI=1S/C46H72N14O10/c1-5-27(4)38(44(69)70)60-41(66)33(14-10-20-53-46(50)51)57-40(65)32(13-9-19-52-45(48)49)58-42(67)34(21-26(2)3)59-43(68)35(23-28-11-7-6-8-12-28)56-37(63)25-54-36(62)24-55-39(64)31(47)22-29-15-17-30(61)18-16-29/h6-8,11-12,15-18,26-27,31-35,38,61H,5,9-10,13-14,19-25,47H2,1-4H3,(H,54,62)(H,55,64)(H,56,63)(H,57,65)(H,58,67)(H,59,68)(H,60,66)(H,69,70)(H4,48,49,52)(H4,50,51,53)/t27-,31-,32+,33+,34?,35+,38-/m0/s1
InChI KeyWRPLGMBDXVBPEG-PUGOIMMUSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentOligopeptides
Alternative Parents
Substituents
  • Alpha-oligopeptide
  • Tyrosine or derivatives
  • Phenylalanine or derivatives
  • Isoleucine or derivatives
  • Leucine or derivatives
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • N-acyl-l-alpha-amino acid
  • Alpha-amino acid amide
  • Alpha-amino acid or derivatives
  • Amphetamine or derivatives
  • N-substituted-alpha-amino acid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Aralkylamine
  • Phenol
  • N-acyl-amine
  • Fatty acyl
  • Monocyclic benzene moiety
  • Benzenoid
  • Fatty amide
  • Guanidine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Amino acid
  • Amino acid or derivatives
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid
  • Carboximidamide
  • Monocarboxylic acid or derivatives
  • Amine
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Primary amine
  • Primary aliphatic amine
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Source:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.022 g/LALOGPS
logP-1.6ALOGPS
logP-5.5ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)3.56ChemAxon
pKa (Strongest Basic)12.18ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area411.05 ŲChemAxon
Rotatable Bond Count31ChemAxon
Refractivity277.93 m³·mol⁻¹ChemAxon
Polarizability103.91 ųChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0f76-0940000002-23f38a333b1089d81ae5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-3910000100-5f0c41a1206c097214b8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-2910000000-3dc833cd70607d235de5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-1000000139-fcfe2daae4be5408e21cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0btj-6330221469-81f9d09eac75cafc472cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9241213131-f7c3e2144b0c04986d52View in MoNA
Biological Properties
Cellular LocationsNot Available
Biospecimen LocationsNot Available
Tissue LocationsNot Available
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB029213
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound53481552
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available