Deoxynojirimycin and its hexosaminyl derivatives bind to natural killer cell receptors rNKR-P1A and hCD69.
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.
Catelani
Giorgio
G
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno, Pisa, Italy. giocate@farm.unipi.it
D'Andrea
Felicia
F
Griselli
Alessio
A
Guazzelli
Lorenzo
L
Nemcová
Petra
P
Bezouska
Karel
K
Krenek
Karel
K
Kren
Vladimír
V
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
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