The scientific interest on the immunological properties of glycosphingolipids (GSLs) is recently increased on account of the role that they could play as therapeutic agents. An interesting aspect of these properties is the immunomudulating activity reported for a number of GSls. Agelasphins, galactosylceramides isolated from marine sponge Agelas mauritiana, exhibited immunostimulating activity, which was suggested to be related to the interesting in vivo antitumoral properties of these compounds through an activation of the immune system. In our continuing studies on glycolipids from marine sponges we have examined the extracts of four species of the genus Agelas and we have isolated a whole new class of GSLs, characterized by an alpha-galactosyl as the sugar directly linked to the ceramide. All the GSLs isolated were tested for their ability to stimulate T-cell proliferation, and the obtained results suggest that the immunostimulating activity is affected by a specific structural feature of the GSLs, namely glycosylation of the inner sugar at position 2. In fact, all the immunostimulating compounds possess a free 2-OH on the sugar directly linked to the ceramide moiety, while this activity disappears if this position is glycosylated either by an alpha-galactosyl or by an alpha-glucosyl. It remains to be understood whether glycosylated alpha-Gal-GSLs are not active because the binding to the T-cell receptor is prevented by the steric hindrance of the additional sugar, or because the free galactose 2-OH group is directly involved in the binding to the receptor. In an attempt to clarify this point, we have been performing a synthetic program turned to the preparation of a number of analogs modified at the key position 2'. To date, we have developed efficient methodologies to synthesize alpha-Gal-GSLs modified at position 2'. In this communication we will report the total stereoselective synthesys of three new agelasphin-analogues shown below and the results of a study to evaluate their immunomodulating activities.
Stereoselective Synthesis and Immunomodulating Activity of Agelasphin Analogues / L., Barbieri; Costantino, Valeria; E., Fattorusso; Imperatore, Concetta; Mangoni, Alfonso. - STAMPA. - (2004), pp. P49-P49. (Intervento presentato al convegno Advances in Synthetic, Combinatorial and Medicinal Chemistry tenutosi a Moscow, Russia nel 5-8 May 2004).
Stereoselective Synthesis and Immunomodulating Activity of Agelasphin Analogues
COSTANTINO, VALERIA;IMPERATORE, CONCETTA;MANGONI, ALFONSO
2004
Abstract
The scientific interest on the immunological properties of glycosphingolipids (GSLs) is recently increased on account of the role that they could play as therapeutic agents. An interesting aspect of these properties is the immunomudulating activity reported for a number of GSls. Agelasphins, galactosylceramides isolated from marine sponge Agelas mauritiana, exhibited immunostimulating activity, which was suggested to be related to the interesting in vivo antitumoral properties of these compounds through an activation of the immune system. In our continuing studies on glycolipids from marine sponges we have examined the extracts of four species of the genus Agelas and we have isolated a whole new class of GSLs, characterized by an alpha-galactosyl as the sugar directly linked to the ceramide. All the GSLs isolated were tested for their ability to stimulate T-cell proliferation, and the obtained results suggest that the immunostimulating activity is affected by a specific structural feature of the GSLs, namely glycosylation of the inner sugar at position 2. In fact, all the immunostimulating compounds possess a free 2-OH on the sugar directly linked to the ceramide moiety, while this activity disappears if this position is glycosylated either by an alpha-galactosyl or by an alpha-glucosyl. It remains to be understood whether glycosylated alpha-Gal-GSLs are not active because the binding to the T-cell receptor is prevented by the steric hindrance of the additional sugar, or because the free galactose 2-OH group is directly involved in the binding to the receptor. In an attempt to clarify this point, we have been performing a synthetic program turned to the preparation of a number of analogs modified at the key position 2'. To date, we have developed efficient methodologies to synthesize alpha-Gal-GSLs modified at position 2'. In this communication we will report the total stereoselective synthesys of three new agelasphin-analogues shown below and the results of a study to evaluate their immunomodulating activities.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
