Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design.
A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. As a consequence, assays to assess inhibition of lectin binding should necessarily come as close...
| Publicado en: | Histochemistry & Cell Biology Vol. 147; no. 2; pp. 285 - 302 |
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| Autores principales: | , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Feb2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=121186055&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 121186055 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09486143 NQI jtl: Histochemistry & Cell Biology issn: 09486143 maglogo: N pubinfo: dt: Feb2017 vid: 147 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 121186055 144013180 10.1007/s00418-016-1525-5 121186055 ppf: 285 ppct: 17 formats: fmt: @attributes: type: P tig: atl: Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. aug: au: Roy, René Cao, Yihong Kaltner, Herbert Kottari, Naresh Shiao, Tze Belkhadem, Karima André, Sabine Manning, Joachim Murphy, Paul Gabius, Hans-Joachim affil: Pharmaqam and Nanoqam, Department of Chemistry , University du Québec à Montréal , P.O. Box 8888, Succ. Centre-Ville Montreal H3C 3P8 Canada sug: ab: A hallmark of endogenous lectins is their ability to select a few distinct glycoconjugates as counterreceptors for functional pairing from the natural abundance of cellular glycoproteins and glycolipids. As a consequence, assays to assess inhibition of lectin binding should necessarily come as close as possible to the physiological situation, to characterize an impact of a synthetic compound on biorelevant binding with pharmaceutical perspective. We here introduce in a proof-of-principle manner work with sections of paraffin-embedded tissue (jejunum, epididymis) and labeled adhesion/growth-regulatory galectins, harboring one (galectin-1 and galectin-3) or two (galectin-8) types of lectin domain. Six pairs of synthetic lactosides from tailoring of the headgroup (3′- O-sulfation) and the aglycone (β-methyl to aromatic S- and O-linked extensions) as well as three bi- to tetravalent glycoclusters were used as test compounds. Varying extents of reduction in staining intensity by synthetic compounds relative to unsubstituted/free lactose proved the applicability and sensitivity of the method. Flanking cytofluorimetric assays on lectin binding to native cells gave similar grading, excluding a major impact of tissue fixation. The experiments revealed cell/tissue binding of galectin-8 preferentially via one domain, depending on the cell type so that the effect of an inhibitor in a certain context cannot be extrapolated to other cells/tissues. Moreover, the work with the other galectins attests that this assay enables comprehensive analysis of the galectin network in serial tissue sections to determine overlaps and regional differences in inhibitory profiles. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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