178181-75-4

Upstream product

• 137792-66-6 phenyl 6-O-(tert-butyldiphenylsilyl)-3,4-O-isopropylidene-D-galactal 
• 122350-52-1 (4S)-5-benzyloxy-4-(9H-fluoren-9-ylmethoxycarbonylamino)-5-oxopentanoic acid 
• 178181-74-3 benzyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-hydroxypentanoate 
• 214468-40-3 1,2-dihydro-6-O-tert-butyldiphenylsilyl-3,4-O-isopropylidene-α-D-galactopyranoside 

Relevant academic research and scientific papers

Use of acid-labile protective groups for carbohydrate moieties in synthesis of glycopeptides related to type II collagen

β-D-Galactopyranosyl and α-D-glucopyranosyl-β-D-galactopyranosyl moieties carrying silyl, isopropylidene and 4-methoxybenzyl protective groups have been attached to the amino acid 5-hydroxy-L-norvaline. The resulting glycosylated building blocks were used in Fmoc solid-phase synthesis of glycopeptides related to a fragment from type II collagen which is immunodominant in a mouse model for rheumatoid arthritis. The protective groups used for the carbohydrate moieties were completely removed during acid catalyzed cleavage of the glycopeptides from the solid phase under conditions which left the O-glycosidic bonds intact.

T cells recognize a glycopeptide derived from type II collagen in a model for rheumatoid arthritis

Even though most eucaryotic proteins are glycosylated, very little is known on if, or how, the glycans influence essential immunological events such as antigen processing, major histocompatibility complex (MHC) restricted presentation, and recognition by T cells. We have used synthetic glycopeptides to elucidate the specificity of T cell hybridomas, obtained by immunization with the glycoprotein type II collagen in a mouse model for rheumatoid arthritis. To enable these studies, glycosylated and suitably protected derivatives of (5R)-5-hydroxy-L-lysine, and the similar 5-hydroxy- L-norvaline, were prepared and then used in Fmoc solid-phase synthesis of glycopeptides related to the immunodominant fragment from type II collagen, CII(256-270). Evaluation of the synthetic glycopeptides provided evidence that antigen-presenting cells can indeed process glycoproteins to glycopeptides, which elicit a T cell response when presented by class II MHC molecules. A glycopeptide carrying a single β-D-galactosyl residue attached to hydroxylysine at position 264 in the center of the CII(256-270) peptide was recognized by most of the hybridomas in a way involving specific contacts between the carbohydrate and the T cell receptor. The results suggest an explanation for the recent observation that glycosylated type II collagen induces more severe forms of arthritis in the mouse than deglycosylated type II collagen and provide additional knowledge on how rheumatoid arthritis may occur also in humans.

Preparation of a glycopeptide analogue of type II collagen - Use of acid labile protective groups for carbohydrate moieties in solid phase synthesis of O-linked glycopeptides

A glycopeptide analogue of the immunodeficient T cell epitope on type II collagen has been prepared by solid phase synthesis. Preparation of a glycosylated amino acid from two monosaccharide units that carried silyl and isopropylidene protective groups and Fmoc 5-hydroxynorvaline was essential for the synthesis. After assembly of the glycopeptide the carbohydrate protective groups were removed simultaneously with acid catalyzed cleavage from the solid phase.