Efomycine M: an inhibitor of selectins?

Bonin, Arne von; Buchmann, Bernd; Bader, Benjamin; Rausch, Alexandra; Venstrom, Kristine; Schäfer, M. B.; Gründemann, Stephan; Günther, Judith; Zorn, Ludwig; Nubbemeyer, Reinhard; Asadullah, Khusru; Zollner, Thomas M.

doi:10.1038/nm0806-873a

Cited by 10 publications

(7 citation statements)

References 4 publications

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“…Moreover, bimosiamose, a synthetic pan-selectin antagonist, showed only moderate effects in a pilot study in five psoriasis patients, despite efficient inhibition of E-and P-selectin-dependent lymphocyte adhesion in vitro, and a considerable decrease in psoriasis events in a xenotransplantation SCID mouse model of psoriasis [65]. The moderate beneficial effects of bimosiamose and also of other immune cell recirculation blockers could also be explained by their immunomodulatory abilities, such as reduction of inflammation, decreased cytokine and chemokine production, interference with T cell proliferation, and induction of T cell apoptosis [65][66][67].…”

Section: Current Concepts Of the Immunopathogenesis Of Psoriasismentioning

confidence: 99%

The pathogenic role of tissue-resident immune cells in psoriasis

Boyman

Conrad

Tonel

et al. 2007

Trends in Immunology

135

102

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Section: Current Concepts Of the Immunopathogenesis Of Psoriasismentioning

confidence: 99%

The pathogenic role of tissue-resident immune cells in psoriasis

Boyman

Conrad

Tonel

et al. 2007

Trends in Immunology

135

102

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“…The macrodiolide efomycine M ( 1 ) was reported to exhibit significant anti‐inflammatory activity in two different mouse models of psoriasis by interfering with the binding of E‐ and P‐selectins 2. This result was hailed as a new therapeutic approach in the treatment of human inflammatory disorders,3 until, quite recently, von Bonin et al., though confirming the anti‐inflammatory profile of 1 , strongly doubted the reported mode of action 4. In light of this controversy, detailed studies on the structure–activity relationships (SAR) appear appropriate for more insight into the biological profile of the compound 5.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis of Efomycine M

Barth

Mulzer

2007

Angew Chem Int Ed

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“…The combination of NMR methods together with molecular modeling revealed a similarity of the three-dimensional structures of efomycin M and sLe x , and, therefore, it was suggested that efomycin M is a selectin antagonist. This mode of action is still unclear, since one study questioned this mechanism [377] while another study supported it [378]. Later, the total Various quinic acid derivatives (Figure 14c) were designed as non-carbohydrate selectin antagonists using a combination of X-ray and molecular modeling methods [373].…”

Section: Non-carbohydrate Inhibitorsmentioning

confidence: 99%

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

2020

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Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLex is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLex tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde’s two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.

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Efomycine M: an inhibitor of selectins?

Cited by 10 publications

References 4 publications

The pathogenic role of tissue-resident immune cells in psoriasis

The pathogenic role of tissue-resident immune cells in psoriasis

Total Synthesis of Efomycine M

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

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