Linked Life Data

8985782

Source:http://linkedlifedata.com/resource/pubmed/id/8985782

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-5-23
pubmed:abstractText
Attempts were undertaken to develop cyclic beta-casomorphin-5 analogs with improved opioid activity profiles by deletion of the glycine residue in position 5, leading to analogs structurally related to the opioid peptide morphiceptin (H-Tyr-Pro-Phe-Pro-NH2). The tetrapeptide sequence Boc-Tyr(tBu)-D-Xaa-Phe-Yaa-OH (Xaa = Lys, Orn, A2bu; Yaa = Pro in L- or D-configuration) was used to study the influence of ring size and chirality on the yield of cyclization between the omega-amino group of Xaa and the C-terminal carboxyl group. In all cases the cyclization reaction was performed under identical experimental conditions to allow a direct comparison with regard to yield and homogeneity. The reaction products were purified by crystallization and liquid chromatography, and were characterized by HPLC, TLC, electrospray mass spectrometry and 1H-NMR spectroscopy. In none of the reactions performed with the cyclization precursors containing proline in the L-configuration could a cyclic monomer be detected, and the cyclodimer (7-9) was the exclusive product in each case. Cyclodimerization was also the favored reaction in the attempted formation of the 11-membered ring of the cyclic [D-A2bu2, D-Pro4]-morphiceptin analog 12, since only traces of the monomer were found. In the case of both the [D-Lys2, D-Pro4]-analog 10 and the [D-Orn2, D-Pro4]-analog 11, the cyclomonomer/cyclodimer ratio was about 80:20. The cyclic monomers 10 and 11 showed high opioid activity in the mu-receptor-representative guinea pig ileum assay (IC50 = 2-5 nM) and in the delta-receptor representative mouse vas deferens assay (IC50 = 50-60 nM), whereas the potency of the cyclodimers was 2-3 orders of magnitude lower in both in vitro bioassays.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0367-8377
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
495-502
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Cyclic morphiceptin analogs: cyclization studies and opioid activities in vitro.
pubmed:affiliation
Department of Drug Biochemistry, Hans-Knoell-Institute of Natural Product Research Jena, Halle, Saale, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't