Linked Life Data

2543911

Source:http://linkedlifedata.com/resource/pubmed/id/2543911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1989-7-24
pubmed:abstractText
Dermorphin, Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 is an extraordinarily potent and highly mu-selective opioid heptapeptide isolated from amphibian skin. It is unique among peptides synthesized by animal cells in having an amino acid residue in the D-configuration. At least two different preprodermorphin cDNAs were cloned from skin of Phylomedusa sauvagei; their predicted amino acid sequences contained four to five homologous repeats of 35 amino acids, each repeat including one copy of the dermorphin progenitor sequence. Tyr-Ala-Phe-Gly-Tyr-Pro-Ser-Gly, flanked by Lys-Arg at the amino end and by Glu-Ala-Lys-Lys at the carboxyl end [Science (Wash. D. C.) 238:200-202 (1987)]. The D-Ala in position 2 in dermorphin is encoded by a usual Ala codon in the precursor sequence. Of the two prodermorphin molecules, one has a dermorphin copy replaced with a distinct heptapeptide same processing signals. Assuming the same pathway as for the release of dermorphin, processing of this precursor may yield, beside dermorphin, a copy of a new peptide, Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2. We have synthetized this peptide together with its (L-Met2)-counterpart and evaluated their respective opioid receptor selectivity in the mouse vas deferens and guinea pig ileum assays and in rat brain membrane binding assays. Overall, the data collected demonstrate that the putative prodermorphin product Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 named dermenkephalin, behaves as a potent delta opioid agonist exhibiting high affinity and high selectivity for the delta opioid receptor. Prodermorphin, thus, offers a surprising example of an opioid biosynthetic precursor that might simultaneously generate highly potent and fully selective agonists for the mu- (morphine) and the delta (enkephalin) opioid receptors, respectively. In addition, because dermenkephalin has no structural features in common with the sequence of all the hitherto known opioid peptides, it should be a useful tool for identifying conformational determinants for high affinity and selective binding of opioids to the delta receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
774-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:2543911-Amino Acid Sequence, pubmed-meshheading:2543911-Analgesia, pubmed-meshheading:2543911-Animals, pubmed-meshheading:2543911-Binding, Competitive, pubmed-meshheading:2543911-Brain, pubmed-meshheading:2543911-Cell Membrane, pubmed-meshheading:2543911-Cerebral Ventricles, pubmed-meshheading:2543911-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:2543911-Enkephalin, D-Penicillamine (2,5)-, pubmed-meshheading:2543911-Enkephalins, pubmed-meshheading:2543911-Injections, Intraventricular, pubmed-meshheading:2543911-Kinetics, pubmed-meshheading:2543911-Male, pubmed-meshheading:2543911-Mice, pubmed-meshheading:2543911-Oligopeptides, pubmed-meshheading:2543911-Opioid Peptides, pubmed-meshheading:2543911-Pain, pubmed-meshheading:2543911-Rats, pubmed-meshheading:2543911-Receptors, Opioid, pubmed-meshheading:2543911-Receptors, Opioid, delta
pubmed:year
1989
pubmed:articleTitle
Dermenkephalin (Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2): a potent and fully specific agonist for the delta opioid receptor.
pubmed:affiliation
Laboratoire de Bioactivation des Peptides, Institut Jacques Monod, Université Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't