| Acid promoted cinnamyl ion mobility within peptide derived macrocycles. | |
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MedLine Citation:
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PMID: 18811162 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We are developing methods that restrict the conformational mobility of peptides and related heteropolymers while simultaneously altering their properties. Our experiments occur as processes wherein a conserved, lipophilic reagent is activated in stages to form composite products with unprotected polyamides in parallel. For each starting oligomer, the goal is to create not one, but rather a collection of products. The intent is for those materials to retain molecular recognition elements of the biopolymer, yet display that functionality as part of stable, cyclic structures having defined shapes and enhanced membrane solubility/permeability. Here we describe reagent 2 and its two-step integration into peptides to afford macrocyclic ethers (e.g., 4 when starting with W-W-Y). When those materials are treated with protic acid in anhydrous solvent, the cinnamyl unit migrates from the oxygen of tyrosine to distribute throughout the structure, forming new products via carbon/carbon bonding. These changes occur concomitantly with acid-promoted rearrangements/cyclizations of the dienyne appendage to generate mixtures containing unique macrocycles such as 15. Similar amalgamations of 2 with more diverse peptides is a means to begin accessing complex peptidomimetics systematically. From a library of screening fractions generated in this way, we have identified a small molecule that selectively promotes hippocampal neurogenesis in the adult mouse brain. |
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Authors:
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Hongda Zhao; Lidet Negash; Qi Wei; Thomas G LaCour; Sandi Jo Estill; Emanuela Capota; Andrew A Pieper; Patrick G Harran |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-09-24 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: 130 ISSN: 1520-5126 ISO Abbreviation: J. Am. Chem. Soc. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-15 Completed Date: 2008-12-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: United States |
Other Details:
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Languages: eng Pagination: 13864-6 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acids
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chemistry* Animals Cell Proliferation / drug effects Cinnamates / chemistry* Cyclization Dentate Gyrus / cytology, drug effects Ions / chemistry Macrocyclic Compounds / chemical synthesis*, chemistry, pharmacology Mice Molecular Conformation Peptides / chemistry* Polymers / chemistry Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Acids; 0/Cinnamates; 0/Ions; 0/Macrocyclic Compounds; 0/Peptides; 0/Polymers |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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