title: Deoxynojirimycin and its hexosaminyl derivatives bind to natural killer cell receptors rNKR-P1A and hCD69.
abstract: Deoxynojirimycin (1) and two new related 4-O-hexosaminyl-containing disaccharide mimics, beta-d-TalNAc-(1-->4)-DNJ (4) and beta-d-ManNAc-(1-->4)-DNJ (5), have been studied as agonists of natural killer (NK) cell receptors. As a positive and unexpected result, DNJ (1) displayed a remarkable activation effect towards both NKR-P1A (rat) and CD69 (human) receptors, and a quite similar activity was found for 4 and 5. The synthesis of the two disaccharide mimics is based on an approach that avoids the glycosylation step using known intermediates arising from lactose. The key stage of the synthesis involves the construction of the DNJ unit through an initial C-5 oxidation of the reducing d-glucopyranosyl unit followed by a stereoselective double-reductive aminocyclization of the 1,5-dicarbonyl disaccharide intermediates.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno, Pisa, Italy. giocate@farm.unipi.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Catelani
authors.forename: Felicia
authors.initials: F
authors.lastname: D'Andrea
authors.forename: Alessio
authors.initials: A
authors.lastname: Griselli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Guazzelli
authors.forename: Petra
authors.initials: P
authors.lastname: Nemcová
authors.forename: Karel
authors.initials: K
authors.lastname: Bezouska
authors.forename: Karel
authors.initials: K
authors.lastname: Krenek
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kren
mesh_terms: D017485:1-Deoxynojirimycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D004187:Disaccharides / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006031:Glycosylation; D006595:Hexosamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D037181:Lectins, C-Type / Q000819:agonists / Q000378:metabolism*; D009005:Monosaccharides / Q000737:chemistry; D010084:Oxidation-Reduction; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099192:CD69 Antigens
chemical_list: D017485:1-Deoxynojirimycin; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004187:Disaccharides; D005944:Glucosamine; D006595:Hexosamines; D037181:Lectins, C-Type; D009005:Monosaccharides; D011971:Receptors, Immunologic; D000099192:CD69 Antigens; C553558:Klrb1a protein, rat; C501633:deoxynojirimycine