Cornelis Versluis

Identification of O-acetylated N-acylneuraminic acids by mass spectrometry

A number of O-acetylated N-acylneuraminic acids, isolated from submandibular glands of cow and horse and from horse erythrocytes, have been characterized by mass spectrometry. On the basis of the typical fragmentation patterns of the pertrimethylsilyl derivatives of the methyl esters of the compounds, they were identified as 4-O-acetyl-, 9-O-acetyl-, 4,9-di-O-acetyl-, and 7,9-di-O-acetyl N-acetylneuraminic acid, and 4-O-acetyl-and 9-O-acetyl-N-glycolylneuraminic acid.

Solid-phase syntheses of peptoids using Fmoc-ProtectedN-substituted glycines: the synthesis of (retro)peptoids of leu-enkephalin and substance P

Solid-phase synthesis of oligomeric peptoids can be conveniently achieved by a repetitive cycle consisting of 1) the removal of the Fmoc group and 2) coupling of a N-substituted glycine derivative (a peptoid monomer). This “monomer” method allows the monitored synthesis of relatively large quantities of pure peptoids as well as the translation of in principle any peptide into the corresponding peptoid, illustrated here (below) by the solid-phase synthesis on a peptide synthesizer of the peptoid of substance P.

Structural studies of the methylated, acidic polysaccharide associated with coccoliths of Emiliania huxleyi (lohmann) kamptner

Abstract For the structure analysis of the methylated, acidic polysaccharide associated with the coccoliths of the alga Emiliania huxleyi (Lohmann) Kamptner, the native, the carboxyl-reduced, and the desulphated, carboxyl-reduced polysaccharides have been submitted to methylation analysis. Graded hydrolysis with acid, uronic acid degradation, and periodate oxidation/partial hydrolysis with acid in conjunction with methylation analysis were also applied. The results of the various degradation procedures have led to a proposed structure for the average unit of the polysaccharide. The mannan backbone consists of at least 80% of (1→3)-linked d -mannosyl residues and has many side-chains. The mannan backbone carries ester-bound sulphate groups, terminal d -ribosyl or l -arabinosyl groups, and short side-chains of two or three d -galactosyluronic acid residues. There is also a complex side-chain composed of d -xylose and l -rhamnose, wherein the branched rhamnosyl residues are substituted by 3- O -methyl- d -xylose, 2,3-di- O -methyl- l -rhamnose, a di-( d -galactosyl-uronic acid)- d -xylosyl unit, and an oligosaccharide. The oligosaccharide is composed of 2,3-di- O -methyl- l -rhamnose, 3- O -methyl- d -galacturonic acid, 6- O -methyl- l -mannose, d -galacturonic acid, l -mannose, and l -rhamnose.

Sialic acids in permethylation analysis: preperation and identification of partially O-methylated derivatives of methlyl N-acetyl-N-methyl-β-D-neuraminate methyl glycoside☆

Abstract A set of partially O -methylated derivatives of methyl N - acetyl- N -methyl-β- D -neuraminate methyl glycoside has been prepared as reference compounds for the Incorporation of acylneuraminic acids into methylation analysis. G.1.c.-m.s. data for the O -trimethylsilyl and O -acetyl derivatives of these compounds are described in detail. The various substances give rise to highly characteristic mass-spectrometric fragmentation-patterns.

Essential oils of five Tanacetum vulgare genotypes

Abstract The essential oils of five Tanacetum vulgare genotypes were investigated and their main components identified. Artemisia alcohol, γ-campholenol, davanone, lyratol, lyratyl acetate and 4-thujen-2α-yl acetate have not been reported before as constituents of Tanacetum vulgare . This is the first time that γ-campholenol has been isolated from a natural source. 4-Thujen-2α-yl acetate is a novel compound.

Comparing mass spectrometric characteristics of peptides and peptoids-2

The high-energy collision-induced dissociation (CID) spectra of the [M+H]+ and [M-H]- ions of substance P fragment 6–11, the retropeptide and the corresponding peptoid and retropeptoid were compared. The CID spectra of the [M+H]+ ion of the corresponding (retro)peptide and (retro)peptoid exhibit both B- and Y″-type sequence ions at identicalm/z-values. The differences in the relative abundances of these sequence ions, however, can be related to structural characteristics of the compounds. The fragmentation behaviour of theN-substituted immonium ions differs from that of the immonium ions derived from common amino acids by showing a preferential loss of a CH2=NH imine molecule. This dominant fragmentation reaction is suppressed in the CID spectrum of theN-substituted glutamine immonium ion in favour of a less energy demanding cyclization reaction involving the loss of NH3. The CID spectra of the [M-H]- ions of both peptides and peptoids show C-type ions, which appeared to be more abundant in the spectra of the peptides than in those of the peptoids.C-Terminal ″Z- and Y-type ions are characteristic of the peptides, whereas the peptoid spectra show relatively abundantN-terminal ″B-type ions. Both [M+H]+ and [M-H]- ion CID spectra show loss of amino acid-specific side-chains, which occurs as radical loss in the case of peptides and as molecular loss in peptoids.

Spacer Effects on in vivo Properties of DOTA-Conjugated Dimeric [Tyr3]Octreotate Peptides Synthesized by a “CuI-Click” and “Sulfo-Click” Ligation Method

We report on the SSTR2‐binding properties of a series of four dimeric [Tyr3]octreotate analogues with different spacer lengths (nine, 19, 41, and 57 atoms) between the peptides. Two analogues (9 and 57 atoms) were selected as precursors for the design, synthesis, and biological evaluation of DOTA‐conjugated dimeric [Tyr3]octreotate analogues for tumor targeting. These compounds were synthesized by using a two‐stage click ligation procedure: a CuI‐catalyzed 1,3‐dipolar cycloaddition (“copper‐click” reaction) and a thio acid/sulfonyl azide amidation (“sulfo‐click” reaction). The IC50 values of these DOTA‐conjugated [Tyr3]octreotate analogues were comparable, and internalization studies showed that the nine‐atom 111In‐DOTA‐labeled [Tyr3]octreotate dimer had rapid and high receptor binding. Biodistribution studies with BALB/c nude mice bearing subcutaneous AR42J tumors showed that the 111In‐labeled [Tyr3]octreotate dimer (nine atoms) had a high tumor uptake at 1 h p.i. (38.8±8.3 % ID g−1), and excellent tumor retention at 4 h p.i. (40.9±2.5 % ID g−1). However, the introduction of the extended hydrophilic 57 atoms spacer led to rapid clearance from the circulation; this limited tumor accumulation of the radiotracer (21.4±4.9 % ID g−1 at 1 h p.i.). These findings provide important insight on dimerization and spacer effects on the in vivo properties of DOTA‐conjugated [Tyr3]octreotate dimers.

Neutralization—reionization experiments with a cell containing potassium vapour

Abstract The design, operation and performance of a potassium vapour cell for exothermic neutralization—reionization (NR) experiments using a VG-ZAB-2F mass spectrometer is described. With the new cell it is possible to maintain over a long period of time a sufficiently high and very stable vapour pressure and this enables the acquisition of many noise-free exothermic NR spectra as single scans. Also with the new cell there is no or minimal leakage of the metal vapour to other parts of the mass spectrometer. Features of selected NR mass spectra are discussed. Not only does exothermic neutralization permit the study of highly excited molecules but the method can also be used to differentiate among isomeric ions where other methods fail.

Structural analysis of acidic oligosaccharides derived from the methylated, acidic polysaccharide associated with coccoliths of Emiliania huxleyi (lohmann) kamptner

Abstract A series of acidic oligosaccharides was obtained by graded, acid hydrolysis of the methylated, acidic polysaccharide associated with the coccoliths of the alga Emiliania huxleyi (Lohmann) Kamptner. After fractionation by ion-exchange chromatography, the structures of the oligosaccharides were determined by sugar analysis, g.l.c.-m.s. of the intact, permethylated oligosaccharide-alditols, and methylation analysis. The following oligosaccharides were characterised: α- d -Gal p A-(1→6)-α- d -Man p -(1→3)- d -Man, d -Gal p A-(1→4)- d -Gal p A-(1→6)-Man, d -Gal p A-(1→4)- d -Gal p A-(1→2/6)-Man p -(1→3)-Man, d -Gal p A-(1→4)- d -Gal p A-(1→3)- d -Xyl, d -Gal p A-(1→2)- l -Man p 6Me-(1→4)- d -Gal p A-(1→2)- l -Rha, d -Gal p A-(1→2)-Man p -(1→4)- d -Gal p A-(1→2)- l -Rha, d -Gal p A-(1→2)- l -Rha p -(1→4)- d -Gal p A-(1→2)- l -Rha, d -Gal p A-(1→2)- l -Man p 6Me-(1→4)- d -GalA, d -Gal p A-(1→2)-Man p -(1→4)- d -GalA, d -Gal p A-(1→2)- l -Man p 6Me-(1→4)- d -Gal p A-(1→2)- l -Man6Me, d -Gal p A-(1→2)- l -Man p 6Me-(1→4)- d -Gal p A-(1→2)-Man, d -Gal p A3Me-(1→2)- l -Man p 6Me-(1→4)- d -Gal p A-(1→2)- l -Man6Me, and d -Gal p A3Me-(1→2)- l -Man p 6Me-(1→4)- d -GalA.

Mass spectrometry of sialic acids

Acyl derivatives of neuraminic acid (5-amino-3, 5-dideoxy-Dglycero-D-galactononulosonic acid) are widespread in animals as well as in microorganisms. The amino function is acetylated or glycolylated (Fig. 1) (1). The hydroxyl functions can be acetylated (2), glycolylated (3), lactylated (4, 5), methylated (6–8) or sulphated (9). The labile neuraminic acid as such does not occur in nature. In literature the term “sialic acids” is used to comprise the family of naturally occurring neuraminic acid derivatives.