Document Detail

Metabolism of diazirine-modified N-acetylmannosamine analogues to photo-cross-linking sialosides.
MedLine Citation:
PMID:  21838313     Owner:  NLM     Status:  MEDLINE    
Terminal sialic acid residues often mediate the interactions of cell surface glycoconjugates. Sialic acid-dependent interactions typically exhibit rapid dissociation rates, precluding the use of traditional biological techniques for complex isolation. To stabilize these transient interactions, we employ a targeted photo-cross-linking approach in which a diazirine photo-cross-linker is incorporated into cell surface sialylated glycoconjugates through the use of metabolic oligosaccharide engineering. We describe three diazirine-modified N-acetylmannosamine (ManNAc) analogues in which the length of the linker between the pyranose ring and the diazirine was varied. These analogues were each metabolized to their respective sialic acid counterparts, which were added to both glycoproteins and glycolipids. Diazirine-modified sialic acid analogues could be incorporated into both α2-3 and α2-6 linkages. Upon exposure to UV irradiation, diazirine-modified glycoconjugates were covalently cross-linked to their interaction partners. We demonstrate that all three diazirine-modified analogues were capable of competing with endogeneous sialic acid, albeit to varying degrees. We found that larger analogues were less efficiently metabolized, yet could still function as effective cross-linkers. Notably, the addition of the diazirine substituent interferes with metabolism of ManNAc analogues to glycans other than sialosides, providing fidelity to selectively incorporate the cross-linker into sialylated molecules. These compounds are nontoxic and display only minimal growth inhibition at the concentrations required for cross-linking studies. This report provides essential information for the deployment of photo-cross-linking analogues to capture and study ephemeral, yet essential, sialic acid-mediated interactions.
Michelle R Bond; Haochi Zhang; Jaekuk Kim; Seok-Ho Yu; Fan Yang; Steven M Patrie; Jennifer J Kohler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-08-25
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  22     ISSN:  1520-4812     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-21     Completed Date:  2012-02-02     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1811-23     Citation Subset:  IM    
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MeSH Terms
Carbohydrate Conformation
Cell Membrane / metabolism
Cholera Toxin / chemistry
Cross-Linking Reagents / chemistry
Cytosol / metabolism
Diazomethane / chemistry
G(M1) Ganglioside / chemistry
Gangliosides / analysis,  chemistry,  metabolism
Glycoconjugates / chemistry,  metabolism
Glycolipids / metabolism
Glycoproteins / metabolism
Hexosamines / chemistry*,  metabolism*
Jurkat Cells
N-Acetylneuraminic Acid / chemistry
Sialic Acid Binding Ig-like Lectin 2 / metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Structure-Activity Relationship
Ultraviolet Rays
Grant Support
Reg. No./Substance:
0/Cross-Linking Reagents; 0/Gangliosides; 0/Glycoconjugates; 0/Glycolipids; 0/Glycoproteins; 0/Hexosamines; 0/Sialic Acid Binding Ig-like Lectin 2; 37758-47-7/G(M1) Ganglioside; 4773-29-9/N-acetylmannosamine; 60A625P70P/Diazomethane; 9012-63-9/Cholera Toxin; GZP2782OP0/N-Acetylneuraminic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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