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J Lutz

Publications and source records attributed to J Lutz.

156 records · Page 9Linked to original sources
PubMedDate not supplied

Peptide/benzodiazepine hybrids as ligands of CCK(A) and CCK(B) receptors.

The (neuro)hormones gastrin and cholecystokinin (CCK) share a common C-terminal tetrapeptide amide sequence that has been recognized as the message portion while the N-terminal extensions are responsible for the CCK(A) and CCK(B) receptor subtype selectivity and avidity. 1,4-Benzodiazepine derivatives are potent and selective antagonists of these receptors, and according to comparative molecular field analysis, the structures of these nonpeptidic compounds could well mimic the message sequence of the peptide agonists at least in terms of spatial array of the aromatic residues. Docking of a larger series of low molecular weight nonpeptide antagonists to a homology modeling derived CCK(B) receptor structure revealed a consensus binding mode that is further validated by data from site-directed mutagenesis studies of the receptors. Whether this putative binding pocket of the nonpeptide antagonists is identical to that of the message portion of the peptide agonists, or whether it is distinct and spatially separated, or overlapping, but with distinct interaction sites, is still object of debate. Using a 1,4-benzodiazepine core amino-functionalized at the C3 position, related tryptophanyl derivatives were synthesized as mimics of the tetrapeptide and subsequently extended N-terminally with gastrin and CCK address sequences. All hybrid constructs were recognized as antagonists by the CCK(A) and CCK(B) receptors, but their address portions were incapable of enhancing in significant manner selectivity and avidity. Consequently, the binding of the peptide/benzodiazepine hybrids has to be dictated mainly by the benzodiazepine moiety, which apparently prevents optimal interactions of the address peptides with extracellular receptor subdomains. These findings would strongly support the view of distinct binding sites for the message portion of the peptide agonists and the benzodiazepine-based nonpeptide antagonists.

Benzodiazepines↗
PubMedDate not supplied

Metal ion binding affinities of gastrin and CCK in membrane mimetic environments.

The fully active gastrin and CCK analogues [Nle 15]-gastrin-17 and [Nle, Thr]-CCK-9 were analysed for their Ca2+ and Tb3+ affinities in various membrane mimetic conditions. In TFE both gastrin and CCK exhibited high affinities for calcium and terbium. At saturation level identical metal ion/peptide ratios were determined with Ca2+ and Tb3+, i.e. R = 3 for gastrin and R = 1 for CCK, confirming the very similar coordination properties of the two metal ions. The conformational effects of both metal ions were found to be very similar with a disordering effect in the case of gastrin and a conformational transition to beta-turn type structure in the case of CCK. In order to mimic more properly physiological conditions, similar experiments were performed in the presence of phospholipid bilayers. No interaction of the peptides with the bilayers was observed even in the presence of mmolar Ca2+ concentrations. Induced lipid interaction via N-terminal lipo-derivatization of gastrin and CCK allowed to translocate quantitatively the two hormones into phospholipid bilayers and to examine the effect of extravesicular Ca2+ on the conformation of the peptide headgroups and on their display at the water/lipid interphase. The CCK moiety of the lipo-CCK inserted into phospholipid bilayers interacts with the lipid phase and addition of Ca2+ enhances the clustering of the peptide headgroups in a more beta-sheet type conformation. Conversely, insertion of lipo-gastrin into the bilayers leads to full exposure of the gastrin headgroup to the bulk water in predominantly random coil structure. Again Ca2+ provokes aggregation. As the lipo-peptide/phospholipid system still represents only an artificial model, it remains hazardous to derive a biological relevance from these data. The significantly higher affinity of lanthanide ions than Ca2+ for the peptides could well play a role in the inhibitory activity of lanthanum on the signal transduction of the CCK family of hormones.

Amino Acid Sequence↗
PubMedDate not supplied

Allopurinol has immunomodulating activity following topical and systemic application in experimental autoimmune uveitis.

PURPOSE: Allopurinol has beneficial effects in the systemic treatment of lens-induced uveitis and experimental autoimmune uveitis (EAU). This is believed to be due to a reduction of oxidative tissue damage through its dose-dependent free radical scavenging ability, and to an immunomodulating effect. The purpose of this study was to demonstrate the immunological effects on the IgG-antibody repertoire in EAU after topical and systemic allopurinol and steroids. METHODS: We assigned 43 male Lewis rats to 6 different groups: healthy rats (BASE, n=3)

Adjuvants, Immunologic↗
PubMedDate not supplied

Community partnership. A school of nursing creates nursing centers for older adults.

A southeastern university school of nursing responded to a request by a local housing authority to provide nursing care and health promotion to the residents of three high-rise complexes for independent living for seniors. This service-learning partnership offers differing educational benefits to graduate and undergraduate nursing students while helping residents remain as well as possible.

Aged↗