| Design and concise synthesis of fully protected analogues of l-gamma-carboxyglutamic acid. | |
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MedLine Citation:
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PMID: 16958524 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The design and synthesis of four nonnaturally occurring amino acid analogues of l-gamma-carboxyglutamic acid (Gla), appropriately protected for Fmoc-based solid-phase peptide synthesis (SPPS), is described. These amino acids are Bu-Mal 2, BCAH 3, Pen-Mal 4, and Cm-Gla 5. These Gla analogues have been designed to replace the glutamic acid of position 1 in the cyclic decapeptide G1TE, which is a potent inhibitor of tyrosine kinase, to further enhance binding to the Grb2-SH2 domain of signal transduction receptors. In the new amino acids, the propionic acid side chain of Glu has been replaced by a malonyl or a carboxymethylmalonyl moiety located at different distances from the alpha-carbon to optimize interactions in the phosphotyrosine-binding cavity of the Grb2-SH2 domain. Additionally, a direct and efficient synthetic route for the preparation of Fmoc-protected l-gamma-carboxyglutamic acid, which is amenable to large-scale production, has been developed to provide this important and unique amino acid(1) in 55% overall yield. |
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Authors:
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Sheng Jiang; Peng Li; Christopher C Lai; James A Kelley; Peter P Roller |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: The Journal of organic chemistry Volume: 71 ISSN: 0022-3263 ISO Abbreviation: J. Org. Chem. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-09-08 Completed Date: 2007-08-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985193R Medline TA: J Org Chem Country: United States |
Other Details:
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Languages: eng Pagination: 7307-14 Citation Subset: IM |
Affiliation:
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Laboratory of Medicinal Chemistry, CCR, NCI-Frederick, NIH, Frederick, Maryland 21702, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Carboxyglutamic Acid*
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analogs & derivatives,
chemical synthesis,
chemistry Molecular Structure Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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53445-96-8/1-Carboxyglutamic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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