Clinical value of serum glycoprotein galactosyltransferase levels in different histological types of ovarian carcinoma.

Serum glycoprotein galactosyltransferase levels were determined in 28 healthy women and 113 patients with ovarian carcinoma with various histological types, at different clinical stages. Ovomucoid, which possesses terminal N-acetylglucosaminyl residues, was used as glycoprotein acceptor. Clinical correlations between galactosyltransferase levels and tumor burden were examined, as well as the variations due to histology. Follow-up studies could be done for 60 patients, and correlations with clinical evolution, established. Galactosyltransferase might be a promising marker for the diagnosis and follow-up of ovarian carcinomas.

Synthesis and evaluation of diastereoisomeric alkylating pseudo-disaccharides as potential affinity reagents for trehalase.

Reaction of (+/-)-(3/4,5,6)-4-bromo-5,6-epoxy-3-hydroxycyclohexene with 2,3,4,6-tetra-O-acetyl-1-thio-alpha-D-glucopyranose, followed by treatment of the resulting isolated diastereoisomeric 4-bromo-3,5-dihydroxycyclohexene 1-thioglycoside derivatives with base under phase-transfer conditions, gave (R)- and (S)-(3,4,6/5)-3,4-epoxy-6-S-(1-thio-alpha-D-glucopyranosyl)-5- hydroxycyclohexene. None of them was substrate or inhibitor for cockchafer trehalase.

Conformations in solution of alpha,alpha-trehalose, alpha-D-glucopyranosyl alpha-D-mannopyranoside, and their 1-thioglycosyl analogs, and a tentative correlation of their behaviour with respect to the enzyme trehalase.

The conformation in solution of alpha-D-glucopyranosyl alpha-D-glucopyranoside (alpha,alpha-trehalose, 1), alpha-D-glucopyranosyl alpha-D-mannopyranoside (3) and their corresponding 1-thioglycosyl analogs, alpha-D-glucopyranosyl 1-thio-alpha-D-glucopyranoside (1-thio-alpha,alpha-trehalose, 2) and alpha-D-glucopyranosyl 1-thio-alpha-D-mannopyranoside (4) were established from high-resolution 1H-NMR and 13C-NMR measurements. These experimental results are in good agreement with the conformations as inferred from hard-sphere calculations. The dihedral angles phi H and psi H are not significantly different for the O-glycosyl disaccharides 1 and 3 compared with their 1-thioglycosyl analogs 2 and 4; however, the internuclear H-1--H-1' and H-1--H-5' distances appear to be longer for 1-thiodisaccharides. This may account for the differences in affinities of cockchafer trehalase which have been observed. This enzyme exhibits less affinity for the competitive inhibitor alpha-D-glucopyranosyl 1-thio-alpha-D-mannopyranoside (4) than for its O-glycosyl analog 3 (Ki 0.055 mM versus 0.0057 mM). From the similarity in Ki between 1-thio-alpha, alpha-trehalose and alpha-D-glucopyranosyl 1-thio-alpha-D-mannopyranoside (0.050 mM versus 0.055 mM), it is possible to assume a similar decrease in the enzymic affinity between the natural substrate (1) and the corresponding 1-thioglycosyl inhibitor (2), which can together be ascribed to the aforementioned difference in the conformation of the molecules.

Comparative specificities of trehalases from various species.

1. Using derivatives or non-symmetrical analogs of alpha,alpha-trehalose, we studied the catalytic specificities of trehalases from various species: Pseudomonas fluorescens, Melolontha vulgaris, porcine and human kidneys. 2. alpha,Beta-trehalose, beta,beta-trehalose, 6,6'dideoxy alpha,alpha-trehalose, alpha-D-xylopyranosyl alpha-D-xylopyranoside were shown to be neither substrates nor inhibitors. 3. 6'deoxy alpha,alpha-trehalose, alpha-D-glucopyranosyl alpha-D-xylopyranoside, alpha-D-allopyranosyl alpha-D-glucopyranoside and alpha-D-galactosyl alpha-D-glucopyranoside, which all possess an intact alpha-D-glucopyranosyl residue, were split by all these trehalases. 4. alpha-D-glucopyranosyl alpha-D-mannopyranoside, alpha,alpha-trehalosamine are competitive inhibitors. 5. These results show the importance of the primary alcohol group at C-6, of the equatorial configuration of the OH groups at C-2, C-3 and C-4 and of the modification of the structure at C-2 of the substrate for the catalytic activity.