Dynamic properties of biologically active synthetic heparin-like hexasaccharides

Angulo, Jesús; Hricovíni, Miloš; Gairì, Margarida; Guerrini, Marco; Paz, José L. de; Ojeda, Ricardo A.; Martín‐Lomas, Manuel; Nieto, Pedro M.

doi:10.1093/glycob/cwi091

Cited by 33 publications

(38 citation statements)

References 28 publications

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“…The sulfated regions of heparin are similar to HS of HSPG. The use of oligosaccharides has already been validated as a good model to replace longer HS chains (44). Indeed, many structural and biological studies using oligosaccharides were consistent with the in vivo biological data (36,45).…”

Section: Discussionmentioning

confidence: 64%

Structural and Functional Characterization of the Interaction between Cyclophilin B and a Heparin-derived Oligosaccharide

Hanoulle

Melchior

Sibille

et al. 2007

Journal of Biological Chemistry

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The chemotaxis and integrin-mediated adhesion of T lymphocytes triggered by secreted cyclophilin B (CypB) depend on interactions with both cell surface heparan sulfate proteoglycans (HSPG) and the extracellular domain of the CD147 membrane receptor. Here, we use NMR spectroscopy to characterize the interaction of CypB with heparin-derived oligosaccharides. Chemical shift perturbation experiments allowed the precise definition of the heparan sulfate (HS) binding site of CypB. The N-terminal extremity of CypB, which contains a consensus sequence for heparin-binding proteins was modeled on the basis of our experimental NMR data. Because the HS binding site extends toward the CypB catalytic pocket, we measured its peptidyl-prolyl cis-trans isomerase (PPIase) activity in the absence or presence of a HS oligosaccharide toward a CD147-derived peptide. We report the first direct evidence that CypB is enzymatically active on CD147, as it is able to accelerate the cis/trans isomerization of the Asp 179 -Pro 180 bond in a CD147-derived peptide. However, HS binding has no significant influence on this PPIase activity. We thus conclude that the glycanic moiety of HSPG serves as anchor for CypB at the cell surface, and that the signal could be transduced by CypB via its PPIase activity toward CD147.First characterized as the molecular targets of the immunosuppressive drug cyclosporin A (CsA), 3 cyclophilins (Cyps) constitute one class of the prolyl cis/trans isomerases that catalyze the cis/trans interconversion of the peptide bond preceding a proline (1, 2). Members of this class such as the predominantly cytoplasmic CypA, the secreted CypB, and the mitochondrial CypD are small ubiquitous proteins sharing a high sequence homology (65% identity between human CypA and CypB), that translates into a closely related three-dimensional fold. Indeed, the NMR and crystal structures of CypA free and in complex with CsA (3-6), as well as the crystal structure of CypB in complex with a cyclosporine analogue (7) all show the same core structure composed of eight antiparallel ␤-strands forming a ␤-barrel surrounded by ␣-helices and loops. Whereas the nearly identical active site and CsA binding pocket further underscore their close relationship, both proteins do differ in their N and C termini, CypB containing two peptides of some 10 residues long that are lacking in CypA.CypA and CypB act in the progression of inflammatory diseases such as rheumatoid arthritis and psoriasis, but are equally involved in the first steps of certain viral infections (8 -10). Their inflammatory activity is conditioned by their interaction with heparan sulfate proteoglycans (HSPGs) and the membrane receptor CD147, two binding partners at the cell surface of T cell lymphocytes, granulocytes and macrophages (11-14). Significantly, both molecular partners have equally been described as co-receptors for the HIV-1 virus (10,12,15).Both intact prolyl cis/trans activity of the cyclophilins and the presence of the Pro 180 residue of CD147, located on one of the two ex...

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Section: Discussionmentioning

confidence: 64%

Structural and Functional Characterization of the Interaction between Cyclophilin B and a Heparin-derived Oligosaccharide

Hanoulle

Melchior

Sibille

et al. 2007

Journal of Biological Chemistry

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“…The first such "one-sided" heparin-like oligosaccharide, an octamer (de Paz et al, 2001), was found to be effective in activating FGF-1, indicating that the trans-dimeric FGF-1/heparin structure may not be necessary for activation (Angulo et al, 2004). The solution conformations and dynamics of the oligosaccharides have been characterized in some detail, and as expected, they behave in a highly anisotropic manner in solution, characteristic of heparin sequences (Angulo et al, 2005).…”

Section: E Synthetic Heparinmentioning

confidence: 57%

Pharmacology of Heparin and Related Drugs

Mulloy

Hogwood

Gray

et al. 2016

Pharmacological Reviews

280

255

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“…A ligand/protein ratio of 3.5:1 was set for OCTA-2, -3, and -4, and a ratio of 5:1 was set for OCTA-1. The correlation time of AT was considered as isotropic and estimated from published data ( AT , 46 ns) (15), whereas an average correlation time value characteristic of oligosaccarides having similar structure was used for octasaccharides ( octasaccharide , 0.9 ns) (28).…”

Section: Methodsmentioning

confidence: 99%

Antithrombin-binding Octasaccharides and Role of Extensions of the Active Pentasaccharide Sequence in the Specificity and Strength of Interaction

Guerrini

Guglieri

Casu

et al. 2008

Journal of Biological Chemistry

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Dynamic properties of biologically active synthetic heparin-like hexasaccharides

Cited by 33 publications

References 28 publications

Structural and Functional Characterization of the Interaction between Cyclophilin B and a Heparin-derived Oligosaccharide

Structural and Functional Characterization of the Interaction between Cyclophilin B and a Heparin-derived Oligosaccharide

Pharmacology of Heparin and Related Drugs

Antithrombin-binding Octasaccharides and Role of Extensions of the Active Pentasaccharide Sequence in the Specificity and Strength of Interaction

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