Synthesis of 0-(2-0-α-d-glucopyranosyl)-β-d-galactopyranoside of optically pure δ-hydroxy-l-lysylglycine and -gd-hydroxy-l-lysylglycyl-l-glutamyl-l- aspartylglycine

Koeners, H. J.; Schattenkerk, Cecile; Verhoeven, Jeroen; Boom, Jacques H. van

doi:10.1016/s0040-4020(01)98942-2

Cited by 32 publications

(5 citation statements)

References 24 publications

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“…The modifications consisted of the sequential monodeoxygenation of the four hydroxy groups on the galactose moiety and the inversion of the stereochemistry at C‐4 (i.e., by using D ‐glucose). Published methods for the synthesis of glycosylated derivatives of hydroxylysine have often involved the use of acid‐labile protecting groups on the carbohydrate moiety 19, 23, 24. Glycosides of deoxygenated sugars are, however, substantially more susceptible to acid‐catalyzed degradation than their nondeoxygenated counterparts 25.…”

Section: Resultsmentioning

confidence: 99%

Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma

Ohno

Yoshinaga

Fujita

et al. 2001

Cancer

117

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Five protected analogues of β‐D‐galactosyl‐(5R)‐5‐hydroxy‐L‐lysine were prepared, in which the galactosyl moiety was modified by monodeoxygenation or inversion of stereochemistry at C‐4. The building blocks were used in the solid‐phase synthesis of a set of glycopeptides related to the peptide fragment CII256–273 from type II collagen. Evaluation of the glycopeptides revealed that T‐cell hybridomas obtained in collagen‐induced arthritis (CIA), which is a common mouse model for rheumatoid arthritis, recognized the galactosyl moiety with high specificity for individual hydroxy groups. Moreover, T‐cell hybridomas obtained in a humanized variant of CIA were also found to recognize the glycopeptides in an equally carbohydrate‐specific manner. The results allowed the generation of models of the complexes formed between the appropriate class II major histocompatibility complex (MHC) molecule, glycopeptide, and the T‐cell receptor, that is, of an interaction that is critical for the stimulation of T cells in the arthritis models. In the structural models, peptide side chains anchor the glycopeptide in pockets in the class II MHC molecule, whereas the galactosylated hydroxylysine residue forms the key contacts with the T‐cell receptor. Importantly, the results also suggest that a T‐cell response towards glycopeptide fragments from type II collagen could play an important role in the development of rheumatoid arthritis in humans.

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Section: Resultsmentioning

confidence: 99%

Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma

Ohno

Yoshinaga

Fujita

et al. 2001

Cancer

117

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“…1 H NMR data for glycopeptide 15 in Table ). Previously, dipeptides containing hydroxylysine have been glycosylated and then used for solution synthesis of short glycopeptides, but the present work respresents the first use of a glycosylated building block of hydroxylysine in Fmoc solid-phase synthesis.…”

Section: Resultsmentioning

confidence: 99%

T Cells Recognize a Glycopeptide Derived from Type II Collagen in a Model for Rheumatoid Arthritis

et al. 1998

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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.

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“…Published methods for the synthesis of glycosylated derivatives of hydroxylysine have often involved the use of acid-labile protecting groups on the carbohydrate moiety. [19,23,24] Glycosides of deoxygenated sugars are, however, substantially more susceptible to acid-catalyzed degradation than their nondeoxygenated counterparts. [25] As a consequence, protection with acetyl groups is necessary to prevent degradation during acidcatalyzed cleavage from the solid support of peptides glycosylated with the 6-deoxysugar L-fucose.…”

Section: Synthesis Of Glycosylated Amino Acids and Glycopeptidesmentioning

confidence: 99%

Glycopeptide Specificity of Helper T Cells Obtained in Mouse Models for Rheumatoid Arthritis

et al. 2002

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Synthesis of 0-(2-0-α-d-glucopyranosyl)-β-d-galactopyranoside of optically pure δ-hydroxy-l-lysylglycine and -gd-hydroxy-l-lysylglycyl-l-glutamyl-l- aspartylglycine

Cited by 32 publications

References 24 publications

Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma

Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma

T Cells Recognize a Glycopeptide Derived from Type II Collagen in a Model for Rheumatoid Arthritis

Glycopeptide Specificity of Helper T Cells Obtained in Mouse Models for Rheumatoid Arthritis

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