[Immunohistochemical examination of MSH2, PMS2, MLH1, MSH6 compared with the analysis of microsatellite instability in colon adenocarcinoma].

Adenocarcinoma of the colon in 10-20% is associated with microsatellite instability, which can occur both in sporadic cancers and in hereditary nonpolyposis colon cancer. Our analysis of 195 cases of adenocarcinoma of the colon showed that microsatellite instability (MSI-H) was found only in 1.5% of patients. Subsequent choice of patients with suspected hereditary Lynch syndrome led to the identification of additional 17 patients with microsatellite instability. They passed an analysis of genes of repair system of unpaired nucleotides of DNA. The study showed that immunohistochemical staining of MSH2, MSH6, MLH1, PMS2 could effectively conduct a preliminary screening of the Lynch syndrome but was unable to divide cases of sporadic and hereditary MSI-H colon cancer.

Preparative route to glucuronyl donors bearing temporary protecting group at O-3 via 6,3-lactonisation by Bz(2)O or Piv(2)O.

Heating of non-substituted beta-D-glucopyranuronic acids in the presence of pivalic or benzoic anhydride in DMF gives 4-O-monoacylated or 2,4-di-O-acylated 6,3-lactones that can be easily transformed into corresponding methyl uronates bearing free OH-groups at C-2 and C-3 or C-3 only, respectively. This method was used for preparation of selectively 3-O-protected glucuronyl donors of thioglycoside and trichloracetimidate types.

Synthesis of 3-O-sulfoglucuronyl lacto-N-neotetraose 2-aminoethyl glycoside and biotinylated neoglycoconjugates thereof.

The 2-aminoethyl glycoside of pentasaccharide 3-O-sulfo-GlcA(beta-1-->3)Gal(beta-1-->4)GlcNAc(beta-1-->3)Gal(beta-1--> 4)Glc(beta (1) and its conjugates with biotin and biotinylated polyacrylic acid were synthesized as molecular probes to investigate the recognition of the HNK-1 epitope containing carbohydrates by proteins. Key steps in the first of two investigated schemes for the preparation of the target compound 1 were (a) assembling of the pentasaccharide backbone (compound 10) by glycosylation of selectively substituted allyl glycoside of the trisaccharide GlcNAc(beta-1-->3)Gal(beta-1-->4)Glc(beta with glucuronyl-galactose glycosyl donor, (b) transformation of the allyl aglycon in 10 into 2-azidoethyl one (to give 11), (c) selective deprotection of the OH group at C-3 of the GlcA residue in 11 via saponification, intramolecular formation of 6,3-lacton (13) and its methanolysis, and (d) subsequent O-sulfation. The alternative scheme with the use of 2-azido-ethyl glycoside of the trisaccharide GlcNAc(beta-1-->3)Gal(beta-1-->4)Glc(beta instead of the allyl glycoside 6 was less effective due to smaller yield at the step of pentasaccharide synthesis. Additionally to 1 the 2-aminoethyl glycosides of the oligosaccharides GlcA(beta-1-->3)Gal(beta-1-->4)GlcNAc(beta-1-->3)Gal(beta-1-->4)Glc(beta, 3-O-sulfo-GlcA(beta-1-->3)Gal(beta, and GlcA(beta-1-->3)Gal(beta were also synthesized.

[Synthesis of oligosaccharides related to HNK-1 antigen. 2. Synthesis of 3'''-O-(3-O-sulfo-beta-D-glucuronopyranosyl)-lacto-N-neotetrao se beta-propylglycoside]. / Sintez oligosakharidov, rodstvennykh antigenu HNK-1. 2. Sintez beta-propilglikozida 3'''-O-sulfo-beta-D-gliukuronopiranozil)-lakto- N-neotetraozy.

A derivative of allyl 3"-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-beta-lactoside with a free OH group at C-4GlcNAc was glycosylated with trichloroacetimidate of selectively protected GlcA(beta 1-->3)Gal alpha disaccharide in dichloromethane in the presence of trimethylsilyl triflate resulting in a pentasaccharide product with an 82% yield. This product was converted to monohydroxy derivative with a free OH group at C-3GlcA via the formation and the subsequent opening of the 6,3-lactone ring in the glucuronic acid residue. The 3"'-O-sulfation of the monohydroxy derivative, the removal of the protective groups, and the reduction of the allyl aglycon yielded the pentasaccharide propyl glycoside NaSO3-3GlcA(beta 1-->3)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc beta-Opr comprising the oligosaccharide chain of the SGGL-1 glycolipid, which is recognized by HNK-1 antibodies. NaSO3-3GlcA(beta 1--> 3)Gal beta OAll, GlcA(beta 1-->3)Gal(beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc beta-OPr and GlcA(beta 1-->3)Gal beta OAll were synthesized in a similar way.

[Synthesis of oligosaccharides related to the HNK-1 antigen. Synthesis of selectively protected allyl-3-o-methyl(beta-D- glucopyranosyl)uronate-beta-D-galactopyranoside]. / Sintez oligosakharidov, rodstvennykh antigenu HNK-1. 1. Sintez izbiratel'no zashchishchennogo allil-3-o-(metil(beta-D-glyukopiranozil)uronat-beta-D- galaktopiranozida.

The glycosylation of several mono- and dihydroxyl glycosyl acceptors based on allyl beta-D-galactopyranoside with completely acylated glucuronyl bromides under the Helferich reaction conditions was studied in order to develop a method for the preparative synthesis of selectively protected disaccharide beta-D-GlcA-(1-->3)-beta-D-Gal in a form that can be used for further preparation of corresponding glycosyl donors and spacerated derivatives. We found that 1,2-orthoesters were the major primary products of the reaction, and their further conversion into isomeric glycosides depended on pH and can be regulated by the type of molecular sieves used. When Acid Washed Molecular Sieves AW 300 were used, glycosides were predominantly synthesized. No selective formation of the (1-->3)-bound disaccharide was observed upon glycosylation of glycosyl acceptors with 2,3- and 3,4-diol groupings. This (1-->3)-bound disaccharide was most efficiently synthesized by glycosylation of allyl 4,6-O-benzylidene-2-O-benzoyl-beta-D-galactopyranoside with pivaloylated glucuronyl bromide. With acetylated or benzoylated glucuronyl bromides or with pivaloyl glucuronyl imidate, this galactoside can also be glycosylated but with a lower yield of the target (1-->3)-bound disaccharide and lower glycosylation regioselectivity.