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rdf:type |
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lifeskim:mentions |
umls-concept:C0014994,
umls-concept:C0026492,
umls-concept:C0220781,
umls-concept:C0282469,
umls-concept:C0449444,
umls-concept:C0449560,
umls-concept:C0597357,
umls-concept:C0678594,
umls-concept:C1510827,
umls-concept:C1704970,
umls-concept:C1709059,
umls-concept:C1883254
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pubmed:issue |
9
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pubmed:dateCreated |
1998-5-21
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pubmed:abstractText |
We show that carbohydrates constitute an attractive source of readily available, stereochemically defined scaffolds for the facile attachment of side chains contained in genetically encoded and other amino acids. beta-D- and beta-L-glucose, L-mannose, and the 6-deoxy-6-N-analogue of beta-D-glucose have been employed to synthesize peptidomimetics that bind the SRIF receptors on AtT-20 mouse pituitary cells, five cloned human receptor subtypes (hSSTRs), and the NK-1 receptor. The affinity profile of various sugar-based ligands at the hSSTRs is compared with that of SRIF. Compound 19 bound hSSTR4 with a Ki of 100 nM. Subtle structural changes affect affinities. Evidence is presented that suggests that one compound (8) binds both the AtT-20 cell receptors and the five hSSTRs via a unique mode. The SARs of the glycosides at SRIF receptors differ markedly from those at the NK-1 receptor. For example a 4-benzyl substituent is important for SRIF receptor binding, but the 4-desbenzyl analogue 27 was highly potent (IC50 of 27 nM) at the NK-1 receptor. A new, nonbasic method for the synthesis of base-sensitive ethers from primary and secondary alcohols is also described.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ethers,
http://linkedlifedata.com/resource/pubmed/chemical/Glucosides,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Monosaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Somatostatin,
http://linkedlifedata.com/resource/pubmed/chemical/Somatostatin,
http://linkedlifedata.com/resource/pubmed/chemical/cyclo(Pro-Phe-Trp-Lys-Thr-Phe)
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BarbosaJJ,
pubmed-author:Cichy-KnightM AMA,
pubmed-author:HirschmannRR,
pubmed-author:HynesJJJr,
pubmed-author:LiuJJ,
pubmed-author:Pietranico-ColeSS,
pubmed-author:RohrerSS,
pubmed-author:ShakespeareW CWC,
pubmed-author:SmithA BAB3rd,
pubmed-author:SpoorsP GPG,
pubmed-author:SprengelerP APA,
pubmed-author:YanVV,
pubmed-author:van RijnR DRD
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1382-91
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9554871-Animals,
pubmed-meshheading:9554871-CHO Cells,
pubmed-meshheading:9554871-Cell Line,
pubmed-meshheading:9554871-Cricetinae,
pubmed-meshheading:9554871-Ethers,
pubmed-meshheading:9554871-Glucosides,
pubmed-meshheading:9554871-Humans,
pubmed-meshheading:9554871-Ligands,
pubmed-meshheading:9554871-Lysine,
pubmed-meshheading:9554871-Mice,
pubmed-meshheading:9554871-Models, Molecular,
pubmed-meshheading:9554871-Molecular Mimicry,
pubmed-meshheading:9554871-Monosaccharides,
pubmed-meshheading:9554871-Peptide Fragments,
pubmed-meshheading:9554871-Pituitary Gland,
pubmed-meshheading:9554871-Receptors, Cell Surface,
pubmed-meshheading:9554871-Receptors, Neurokinin-1,
pubmed-meshheading:9554871-Receptors, Somatostatin,
pubmed-meshheading:9554871-Somatostatin,
pubmed-meshheading:9554871-Stereoisomerism,
pubmed-meshheading:9554871-Structure-Activity Relationship
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pubmed:year |
1998
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pubmed:articleTitle |
Modulation of receptor and receptor subtype affinities using diastereomeric and enantiomeric monosaccharide scaffolds as a means to structural and biological diversity. A new route to ether synthesis.
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pubmed:affiliation |
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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