Linked Life Data

10323556

Source:http://linkedlifedata.com/resource/pubmed/id/10323556

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-6-29
pubmed:abstractText
We report the synthesis, binding affinities to the recombinant human somatostatin receptors, and structure-activity relationship studies of compounds related to the cyclic hexapeptide, c-[Pro6-Phe7-D-Trp8Lys9-Thr10-Phe11], L-363,301 (the numbering in the sequence refers to the position of the residues in native somatostatin). The Pro residue in this compound is replaced with the arylalkyl peptoid residues Nphe (N-benzylglycine), (S)betaMeNphe [(S)-N-[alpha(-methyl)benzyl]glycine] or (R)betaMeNphe [(R)-N-[(alpha-methyl)benzyl]glycine] and L-1-naphthylalanine is incorporated into either position 7 or 11 of the parent compound. The synthesis and binding data of the Nnal6 ([N-naphthylmethyl]glycine) analog of L-363,301 is also reported. The incorporation of the Nnal residue into position 6 of L-363,301 resulted in an analog with weaker binding affinities to all hsst receptors but enhanced selectivity towards the hsst2 receptor compared with the parent compound. The other compounds bind effectively to the hsst2 receptor but show some variations in the binding to the hsst3 and hsst5 receptors resulting in different ratios of binding affinities to the hsst5 and hsst2 or hsst3 and hsst2, respectively. The incorporation of the Nphe residue into position 6 and the Nal residue into position 7 of L-363,301 led to a compound which binds potently to the hsst2 and has increased selectivity towards this receptor (weaker binding to hsst3 and hsst5 receptors) compared with the parent compound. The analogs with beta-methyl chiral substitutions in the aromatic peptoid side chain and Nal in position 7 or 11 bind effectively to the hsst2 and hsst5 receptors. They exhibit similar ratios of binding affinities to the hsst5 and hsst2 receptors as observed for L-363,301. There are however minor differences in binding to the hsst3 receptor among these analogs. These studies allow us to investigate the influence of additional hydrophobic groups on the binding activity to the isolated human somatostatin receptors and the results are important for the design of other somatostatin analogs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1075-2617
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
113-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Synthesis and binding properties of cyclohexapeptide somatostatin analogs containing naphthylalanine and arylalkyl peptoid residues.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of California at San Diego, LaJolla 92093-0343, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't