Linked Life Data

19807094

Source:http://linkedlifedata.com/resource/pubmed/id/19807094

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2009-11-5
pubmed:abstractText
Structural modifications affecting the efficacy of analogues of the endogenous opioid peptide dynorphin (Dyn) A have focused on the N-terminal "message" sequence based on the "message-address" concept. To test the hypothesis that changes in the C-terminal "address" domain could affect efficacy, modified amino acids and cyclic constraints were incorporated into this region of the partial agonist [N-benzylTyr(1)]Dyn A-(1-11). Modifications in the C-terminal domain of [N-benzylTyr(1)]Dyn A-(1-11)NH(2) resulted in increased kappa opioid receptor (KOR) affinity for all of the linear analogues but did not affect the efficacy of these peptides at KOR. Cyclization between positions 5 and 8 yielded [N-benzylTyr(1),cyclo(d-Asp(5),Dap(8))]Dyn A-(1-11)NH(2) (zyklophin, 13) ( J. Med. Chem. 2005 , 48 , 4500 - 4503 ) with high selectivity for KOR. In contrast to the linear peptides, this peptide exhibits negligible efficacy in the adenylyl cyclase (AC) assay and is a KOR antagonist. These data are consistent with our hypothesis that appropriate modifications in the "address" domain of Dyn A analogues may affect efficacy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6814-21
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The effects of C-terminal modifications on the opioid activity of [N-benzylTyr(1)]dynorphin A-(1-11) analogues.
pubmed:affiliation
Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66045, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural