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Biomedical subjects

H Kunz

Publications and source records attributed to H Kunz.

At least 19 recordsLinked to original sources
PubMed1998

Effects of glycosylation on fragments of tumour associated human epithelial mucin MUC1.

The glycodecapeptide AcPAPGS(alpha GalNAc)T(alpha GalNAc)APPA and the C-terminal glycohexapeptide AcS(alpha GalNAc)T(alpha GalNAc)APPA have been synthesized by applying the N-terminal Fmoc group in combination with the heptyl ester cleavable by lipase-catalyzed hydrolysis at pH 7. The solution conformation of these MUC1-related synthetic glycopeptides and the control, non-glycosylated decapeptide AcPAPGSTAPPA have been investigated using NMR spectroscopy. The structural studies indicate that the glycohexapeptide has a folded structure in solution. For this molecule, unrestrained molecular dynamics has been used to confirm the presence of the observed solution through-space connections. The results indicate that the non-globular nature of MUC1 is due to both protein core sequence and the effect of carbohydrate.

Amino Acid Sequence↗
PubMed1998

Synthesis of cyclic dipeptide templates, their incorporation into peptides and studies on their conformational and biological properties.

This study investigated the diastereoselective synthesis of three dipeptide templates 1, 2 and 3, which may be regarded as conformationally restricted analogs of H-Gly-Xaa-OH, in which Xaa constitutes an aromatic amino acid. Bond formation between alpha-C of Gly and the aromatic moiety was achieved by proton-catalyzed intramolecular electrophilic aromatic substitution. The absolute configuration of the dipeptide templates was determined by single-crystal X-ray crystallography or by nuclear Overhauser enhancement measurements. A protective group strategy was elaborated to allow their incorporation into peptide sequences by liquid phase as well as by solid-phase peptide synthesis. The templates were used to generate an enkephalin analog 15, a modified peptidic neurokinin antagonist 20 and two dermorphin derivatives (24 and 33). Molecular dynamic simulations with 15 and 20 revealed the preference for a turn-like motif for 15. The biological activity, as investigated by respective receptor binding and functional assays, was strongly diminished with all four derivatives, indicating that their receptor-relevant molecular geometries lie outside the examined conformational space.

Crystallography, X-Ray↗
PubMed1997

Glycosyl azides as building blocks in convergent syntheses of oligomeric lactosamine and Lewis(x) saccharides.

Oligosaccharides containing type 2 lactosamine repeating units, e.g. neo-lacto-octaose and trimeric Lewis(x) derivatives, are constructed using neo-lactosamine azide building blocks. The azido group provides a favorable protection of the anomeric position which is stable to versatile protecting group manipulations and glycosylation reactions. On the other hand, glycosyl azides can be converted into glycosyl fluorides via a 1,3-dipolar cycloaddition with di-tert-butyl-acetylenedicarboxylate and subsequent treatment of the resulting N-glycosyl triazoles with hydrogen fluoride-pyridine complex. Activation of the lactosamine fluorides with Lewis acids affords the possibility to extend the oligosaccharide chain with disaccharide units. Suitable protecting group combinations within the galactose and the glucosamine portion of the lactosamine unit enable selective deprotection reactions and, subsequently, chain extension or branching, e.g. to yield Lewis(x) structures.

Amino Sugars↗
PubMed1995

Chemical and enzymatic synthesis of glycopeptides.

Progress recently made in the synthesis of biologically relevant N- and O-glycopeptides is illustrated by examples. In this context, developments in the preparation of complex saccharide side chains and in the subsequent coupling to peptide portions is described. Special emphasis is given to the synthesis of Lewis antigen-type structures. Furthermore, modern methods in solid phase peptide syntheses utilizing glycosylated building blocks are presented. Recent advances in glycopeptide syntheses employing enzymatic methods in deprotection steps as well as in peptide/saccharide chain elongation are reported.

Amino Acid Sequence↗
PubMed1994

Synthesis of glycopeptides and neoglycoproteins containing the fucosylated linkage region of N-glycoproteins.

N-Glycoproteins fucosylated in the core region occur in tumor membranes and virus envelopes. Partial structures of such N-glycoproteins containing fucosylated chitobiosyl asparagine conjugates were synthesized using the allyloxycarbonyl (Aloc) and the tert-butyl ester protecting groups in the peptide portion. As the alpha-fucosidic bond of the conjugates revealed to be very sensitive to acids when carrying ether-type protecting groups, a method for exchanging the protecting groups of the fucose portion of saccharides was developed. Conjugates containing O-acetyl protected fucose proved to be stable against acids used in glycopeptide syntheses. These methods were applied in the synthesis of a fucosyl chitobiose hexapeptide with the partial sequence of a leukemia virus envelope glycoprotein. The glycopeptide was coupled to bovine serum albumin yielding a neoglycoprotein which contains a glycoconjugate of exactly specified structure.

Amino Acid Sequence↗
PubMed1994

[Laboratory diagnosis of parvovirus B 19 infection: comparison of ten commercial IgG- and IgM-antibody tests].

Seven ELISAs, two westernblots and one immunofluorescence assay for serological detection of parvovirus-B19-infection were compared with regard to their sensitivity and specificity. All ten assays are commercially available and use recombinant proteins (VP1, VP2) from bacterial and eukaryotic expression systems and synthetic viral peptides as antigens. The ELISA assays comprise indirect ELISA and mu-capture systems. All assays were tested for their sensitivity with follow-up sera from 21 patients with acute parvovirus B19 infections. The specificity was analysed by 194 sera from pregnant women and from patients with acute other virus infections or rheumatoid factors, but without acute parvovirus infection. Only three ELISAs, both westernblots and the immunofluorescence assay can be recommended for the IgG-measuring (prevalence). For the detection of an acute parvovirus infection, especially during pregnancy, two ELISAs show good IgG- and IgM-results, one ELISA is less recommendable and all other assays show only a poor IgM-specificity.

Antibodies, Viral↗
PubMed1993

A new method of anomeric protection and activation based on the conversion of glycosyl azides into glycosyl fluorides.

Glycosyl azides provide reliable anomeric protection stable to conditions for hydrolytic removal of ester groups, for reductive opening or release of acetalic diol protection, for the introduction of ether-type protection, and for glycosylation processes. The utility of this anomeric protection is further enhanced as glycosyl azides may be converted into glycosyl fluorides, which can be activated for glycosylation reactions. To this end, glycosyl azides have been subjected to 1,3-dipolar cycloaddition with di-tert-butyl acetylenedicarboxylate. On treatment with hydrogen fluoride-pyridine complex the N-glycosyl triazole derivatives directly give glycosyl fluorides.

Azides↗
PubMed1992

Synthesis of beta-D-mannosides from beta-D-glucosides via an intramolecular SN2 reaction at C-2.

The selective synthesis of beta-D-mannosides was achieved by first synthesizing beta-D-glucosides that carry a N-phenylcarbamoyl protecting group at O-3. These derivatives were transformed into the corresponding beta-D-mannosides by intramolecular nucleophilic substitution with inversion of configuration at C-2, the O-trifyl group being the leaving group. Subsequent intramolecular attack of the neighboring carbamoyl group resulted in the formation of the 2,3-carbonate of the desired beta-D-mannoside.

Carbohydrate Sequence↗
PubMed1991

Evidence that the fate of class II-disparate corneal grafts is determined by the timing of class II expression.

While the immune privilege nature of the eye affords significant protection to corneal grafts, immunologic rejection is the leading cause of graft failure. Class II antigens are normally absent or expressed at very low levels in normal cornea. The role that class II antigens play in causing graft rejection is particularly interesting. Class II molecules are present on many cells of the immune system, and therefore are important in modulating and mediating immune reactions. The absence of class II bearing cells in the cornea leads to the interesting issue of whether or not those antigens can induce immune rejection of a corneal graft. In the current study we have made use of a pair of congenic rat strains that differ only at class II loci to determine the impact of these antigens on corneal graft survival. Central corneal grafts were not rejected. Recipients preimmunized with skin grafts rejected 100% of the class II disparate corneas with a median survival time (MST) of 15.5 days. When class II disparate Langerhans-cell-containing (LC+) corneas were grafted, the corneas were not rejected, but they immunized the recipients as evidenced by the rejection of a second corneal graft on the contralateral eye. Immunofluorescent stains demonstrated transient expression of class II antigens on graft epithelium after transplantation. This temporary appearance of class II provides a target for rejection in the preimmunized animals but is of insufficient duration to both prime naive animals and provide a target for antigraft effectors.

Animals↗
PubMed1991

New enzymatic protecting group techniques for the construction of peptides and glycopeptides.

The use of non-proteases for the selective removal of protecting groups from peptides and glycopeptides is described. The N-terminal deprotection of peptides can be achieved by the hydrolysis of the phenylacetyl (PhAc) amide blocking group catalyzed by penicillin G acylase. On the other hand, the lipase-mediated hydrolysis of n-heptyl (Hep) and 2-bromoethyl esters allows for the liberation of the C-terminal carboxy group. The selective C-terminal deprotection can be applied advantageously for the construction of acid- and base-sensitive polyfunctional O-glycopeptides. In all cases the enzymatic reactions are completely selective and proceed under mildest conditions (pH 7-8, r.t. to 37 degrees C) without damaging the various other functionalities present in the complex substrates.

Amino Acid Sequence↗
PubMed1990

Synthesis of glycopeptides with the TN and T antigen structures, and their coupling to bovine serum albumin.

Glycopeptides with TN and T antigen structures that represent the N-terminal tripeptide of asialoglycophorin with blood-group M specificity have been synthesized using fluorenylmethoxycarbonyl (Fmoc) and 2-pyridylethoxycarbonyl (Pyoc) groups for amino protection and the benzyl ester as the carboxyl-blocking function. The Fmoc and the Pyoc groups could be removed by treatment with the weak base morpholine under conditions where the base-sensitive O-glycosyl-serine and -threonine linkages were stable. Ester groups were removed from the carbohydrate moieties with methanolic hydrazine, to give the TN and T antigen glycopeptides which were coupled to bovine serum albumin (BSA) via a carbodi-imide procedure and without any spacer groups. The resulting conjugates contained an average of greater than 20 glycopeptides per protein molecule. They are not microheterogeneous in the carbohydrate part as is commonly found for glycoproteins isolated from biological sources.

Antigens, Neoplasm↗
PubMed1990

Synthesis of 2-acetamido-2-deoxyglucosylasparagine glyco-tripeptides and -pentapeptides by selective C- and N-terminal elongation of the peptide chain.

The synthesis of protected 2-acetamido-2-deoxyglucosylasparagine glycopeptides, using the allyl ester as the C-terminal protecting group, their deprotection, and some possible applications of these glycopeptides for the synthesis of modified silica gels and the construction of liposomes are described. The selective carboxyl deblocking is achieved under neutral conditions by rhodium(I)-catalyzed isomerization of the allyl group followed by hydrolysis of the resulting propenyl ester. The tert-butoxycarbonyl group can be cleaved selectively in the presence of the allyl ester with hydrogen chloride in ether. The allyl ester and the acetates can be removed simultaneously with ammonia in methanol. This method opens up a preparative route to glycopeptide model structures of biological interest.

Amides↗
PubMed1990

Synthetic tumor-associated glycopeptide antigens.

Glycopeptides with TN antigen (GalNAc)Ser/Thr and T-antigen structures (beta Gall-3GalNAc)Ser/Thr, described as tumor-associated antigens, were synthesized and coupled to bovine serum albumin. Alternatively, synthetic methods for the construction of beta-anomeric analogues of the TN and T-antigen glycopeptides were developed, aiming at antigenic structures having a varied stereochemistry of the linkage between the carbohydrate and the peptide moiety. As a further type of potential tumor-associated antigen, fucosyl-chitobiose asparagine glycopeptides were synthesized, deprotected, and coupled to bovine serum albumin. The chemical methods developed now make the complex sensitive glycoprotein partial structures accessible in analytically pure form and in preparative amounts.

Amino Acid Sequence↗
PubMed1987

Prophylactic treatment of acute gastroduodenal stress ulceration. Low-dose antacid treatment without and with additional ranitidine.

Low-dose antacid treatment without and with additional ranitidine in the prevention of acute gastroduodenal stress ulceration in high-risk patients was compared in a randomized, double-blind clinical trial with endoscopic examination of the upper gastrointestinal tract before entry and after the 7-day study period. Of 67 patients who entered the study, 56 could be evaluated. Only one patient, allocated to antacid and placebo, had massive acute upper gastrointestinal bleeding, arising from a gastric ulcer. Although gastric intraluminal pH was better controlled with additional ranitidine treatment, the occurrence of mucosal lesions did not depend on the assigned treatment. We conclude that there is no significant difference between the two regimens in terms of endoscopically visible lesions and clinical outcome.

Acute Disease↗