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S Ostergaard

Publications and source records attributed to S Ostergaard.

30 records · Page 2Linked to original sources
PubMed1998

The dominant epitope of Borrelia garinii outer surface protein C recognized by sera from patients with neuroborreliosis has a surface-exposed conserved structural motif.

Epitope mapping of outer surface protein C (OspC) by using sera from patients with neuroborreliosis led to the identification of one single major immunodominant epitope within the C-terminal 10 amino acid residues. Peptide binding studies and alanine replacement scanning of the C-terminal decapeptide, PVVAESPKKP, revealed a critical role for the PKKP sequence and its terminal carboxyl group for the binding of immunoglobulin M (IgM) antibodies from patients with Lyme borreliosis. Electron microscopy of antibody-labeled spirochetes indicated that the C-terminal region is exposed on the surface of the spirochete. Based on homology to proteins of known function, this region most probably adopts a polyproline II-like helix, which is found in surface-exposed structures involved in protein-protein interactions. This structural motif is highly conserved in Borrelia species causing Lyme borreliosis and subjected to purifying selection. We suggest that the abundance of the C-terminal region of OspC on the surface of B. burgdorferi allows a multimeric high-avidity interaction between the spirochete and surface Igs on B cells. The resulting cross-linking of surface Igs on B cells may induce a T-cell-independent B-cell activation without IgM-to-IgG switching, thus explaining the lack of IgG antibodies to OspC in neuroborreliosis.

Adolescent↗
PubMed1997

Analysis of 31 families with an apparently autosomal-dominant transmission of migraine with aura in the nuclear family.

We analyzed 31 families selected for an apparently autosomal-dominant mode of inheritance of migraine with aura (MA) in the nuclear family. The nuclear families were expanded with first- and second-degree relatives. All interviews were made by physicians experienced in headache diagnoses. The criteria of the International Headache Society were used. The population relative risk among children in nuclear families was similar to the estimated population relative risk of MA assuming an autosomal-dominant mode of inheritance. The population relative risk tended to decrease among first-degree relatives outside nuclear families and further among second-degree relatives. Both first- and second-degree relatives outside the nuclear families had a statistically significant lower risk of MA than expected. Thus, autosomal-dominant inheritance with or without reduced penetrance was unlikely. Autosomal-recessive inheritance was unlikely because of the unequal sex distribution. Other modes of inheritance were considered as well. Mitochondrial and X-linked inheritance were excluded because of paternal transmission. The female preponderance was too low to explain sex-influenced inheritance. We conclude that MA most likely has a multifactorial inheritance even in high-risk families with MA.

Adolescent↗
PubMed1997

Peptomers: a versatile approach for the preparation of diverse combinatorial peptidomimetic bead libraries.

This report describes a versatile approach in the generation of peptidomimetic bead libraries. The method is based on the preparation of peptide-peptoid hybrids using the portioning-mixing procedure, which gives diverse peptidomimetic bead libraries composed of peptides, peptoids and peptide-peptoid hybrids. We term these peptomers, from peptide-peptoid hybrid polymers. The synthesis of the peptomers is easily accomplished by adapting the peptoid synthesis strategy, in which a primary amine reacts with bromoacetic acid, and we combine this methodology with conventional peptide synthesis. The sequence of the active compound is deduced by conventional microsequencing using Edman degradation chemistry, thus avoiding the synthesis of a coding structure or the addition of molecular tags. We demonstrate the utility of the peptomer approach by the synthesis of a bead library together with the identification of novel peptidomimetic ligands binding to the macromolecular targets streptavidin and the insulin receptor.

Binding Sites↗
PubMed1996

The 18-kilodalton Chlamydia trachomatis histone H1-like protein (Hc1) contains a potential N-terminal dimerization site and a C-terminal nucleic acid-binding domain.

The Chlamydia trachomatis histone H1-like protein (Hc1) is a DNA-binding protein specific for the metabolically inactive chlamydial developmental form, the elementary body. Hc1 induces DNA condensation in Escherichia coli and is a strong inhibitor of transcription and translation. These effects may, in part, be due to Hc1-mediated alterations of DNA topology. To locate putative functional domains within Hc1, polypeptides Hc1(2-57) and Hc1(53-125), corresponding to the N- and C-terminal parts of Hc1, respectively, were generated. By chemical cross-linking with ethylene glycol-bis (succinic acid N-hydroxysuccinimide ester), purified recombinant Hc1 was found to form dimers. The dimerization site was located in the N-terminal part of Hc1 (Hc1(2-57)). Moreover, circular dichroism measurements indicated an overall alpha-helical structure of this region. By using limited proteolysis, Southwestern blotting, and gel retardation assays, Hc1(53-125) was shown to contain a domain capable of binding both DNA and RNA. Under the same conditions, Hc1(2-57) had no nucleic acid-binding activity. Electron microscopy of Hc1-DNA and Hc1(53-125)-DNA complexes revealed differences suggesting that the N-terminal part of Hc1 may affect the DNA-binding properties of Hc1.

Amino Acid Sequence↗
PubMed1995

Novel avidin and streptavidin binding sequences found in synthetic peptide libraries.

Synthetic resin-bound peptide libraries made of protein L-amino acids have been synthesized. During screening of the libraries, peptides that bind to avidin have been identified containing a novel motif with two histidines separated by one residue. A sub-library was synthesized and screened, and new critical residues appeared surrounding the two histidines. Additionally peptide libraries made of D-amino acids have been screened with avidin and streptavidin and novel motifs have been found.

Amino Acid Sequence↗
PubMedDate not supplied

Synthesis and screening of an indexed motif-library containing non-proteinogenic amino acids.

In an effort to increase the probability of finding novel peptides in resin-bound combinatorial libraries displaying affinity to various macromolecular targets, we increased the diversity of a solid-phase library considerably by synthesizing multiple structures on each bead - a motif-library - including 45 building blocks. The building blocks consist of L-aa, D-aa and eight hydrophobic non-proteinogenic alpha-amino acids. A library with the format O-Z0-1-O-Z0-1-O-XX-resin was synthesized giving the four motifs OOOXX, OZOOXX, OOZOXX, OZOZOXX corresponding to 364.500 different motifs (45(3) x 4 theoretical combinations). The positions O are defined amino acids while Z represents three mixtures pi, omega, phi, where pi is a mixture of polar and charged residues, omega is a mixture of aliphatic residues and phi is a mixture of aromatic residues. X represents a mixture of all 45 residues. The library was screened with the macromolecular target streptavidin which served as a model receptor. Binding peptides were sequenced by microsequencing. We included small amounts of norvaline and norleucine in the library, which served as index residues to be able to distinguish between LD-amino acids and other residues with the same retention time in the HPLC system. Beads that interact with the receptor were found, and the binding motifs that appeared had no homology to known binding motifs found in either L-aa or D-aa libraries, instead motifs with the non-proteinogenic residues L-phenylglycine, O-benzyl-L-hydroxyproline and O-benzyl-L-tyrosine dominated. The novel peptides inhibit binding of biotin to streptavidin but do not bind to avidin, and the affinity is higher than the peptides found in linear all L-aa peptide libraries.

Amino Acids↗
PubMedDate not supplied

Characterization of Chlamydia trachomatis l2-induced tyrosine-phosphorylated HeLa cell proteins by two-dimensional gel electrophoresis.

Chlamydia trachomatis is an obligate intracellular bacteria, inducing its own uptake in nonprofessional phagocytes either by phagocytosis or pinocytosis. We have previously shown that C. trachomatis L2 induces tyrosine phosphorylation of eukaryotic proteins upon their entry by phagocytosis. In this paper we characterize the tyrosine-phosphorylated proteins by two-dimensional gel electrophoresis. In immunoblotting with anti-phosphotyrosine antibodies of C. trachomatis L2-infected HeLa cells, but not with uninfected cells, two rows of spots were observed with a molecular mass of 69 and 71 kDa and pI from 5.0 to 5.2. In addition, a single spot of 100 kDa and pI 6.2 was observed.

Animals↗