Linked Life Data

8759639

Source:http://linkedlifedata.com/resource/pubmed/id/8759639

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1996-9-24
pubmed:abstractText
The application of the concept of backbone cyclization to linear substance P (SP) analogs is presented. We describe the synthesis, characterization, and biological activity of a series of backbone-to-amino-terminus cyclic analogs of the C-terminal hexapeptide of SP. These analogs were designed on the basis of NMR data and molecular modeling of the selective NK-1 analog WS-septide (Ac[Arg6,Pro9]SP6-11). A series of peptides with the general formula: cyclo[-CH2)m-NH-CO-(CH2)n-CO-Arg-Phe-Phe-N-]-CH2-CO-Leu-Met-NH2 (n = 2, 3, 6 and m = 2, 3, 4) was synthesized by solid phase methodology using Fmoc chemistry for the main chain and Boc chemistry for the building units [Na-(omega-aminoalkyl)Gly] side chains. Cyclization was performed on the resin after removal of the Boc protecting group from the omega-aminoalkyl chain. Cyclic and precyclic analogs were compared. They were purified by HPLC and characterized by mass spectroscopy and NMR. Biological activity and selectivity to the NK-1 neurokinin receptor were found to depend on cyclization and the ring size: The most active and selective analog had a ring of 20 atoms. This analog was found to have enhanced metabolic stability in various tissue preparation compared to WS-septide.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3174-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Synthesis and biological activity of NK-1 selective, N-backbone cyclic analogs of the C-terminal hexapeptide of substance P.
pubmed:affiliation
Department of Organic Chemistry, Hebrew University of Jerusalem, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't