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Biomedical subjects

W Brandt

Publications and source records attributed to W Brandt.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cardioactive steroid saponins and other constituents from the aerial parts of Tribulus cistoides.

From the petrol extract of the aerial parts of Tribulus cistoides three steroid sapogenins and two N-acyltyramines were isolated, whereas the methanolic extract gave nine steroid saponins, among them the cardioactive cistocardin, saponin-3, saponin-4 and saponin-7. Furthermore, a furostanol diglycoside was isolated besides 5'-(hydroxysulphonyloxy) jasmonic acid, D-(+)-pinitol and sucrose. The structures were established by spectroscopic investigations of the isolated compounds and their hydrolysis products. 5'-(Hydroxysulphonyloxy) jasmonic acid has been prepared by partial synthesis.

Animals↗
PubMed1994

Classification of serine proteases derived from steric comparisons of their active sites, part II: "Ser, His, Asp arrangements in proteolytic and nonproteolytic proteins".

The assignment of serine proteases to the families of (chymo)trypsins and subtilisins, respectively, is extended by including additional data from the Brookhaven Protein Data Bank. To better understand basic properties connected with this type of assignment the steric situation in the vicinity of the tetrad aminoacyl residues and atomic distances within the tetrads are considered. A new catalytic mechanism is suggested based on differences between tonin and kallikrein with respect to structure and reactivity of the catalytic tetrad. All protein structures available from the Brookhaven Protein Data Bank are analyzed with regard to the occurrence of Asp....His....Ser triads.

Amino Acid Sequence↗
PubMed1993

Is the analgesic activity of epibatidine caused by a chemical reaction with the morphine opioid receptor?

Using the molecular modeling program SYBYL, a conformational analysis of epibatidine has been performed. Two pairs of stable conformations due to the rotational degree of freedom for the pyridine ring have been found. These conformations were compared with morphine regarding spatial arrangements as well as electronic aspects. A very close agreement between the essential receptor positions occurring in morphine and epibatidine could be demonstrated. The protonable nitrogen atom in epibatidine is in exactly the same spatial position as in morphine, if the pyridine ring and the phenolic ring of morphine were matched to each other. Interestingly, it is also apparent that the pyridine nitrogen atom is in a close position to the bridging oxygen atom of morphine. Furthermore, the chlorine substituent fits very well with the hydroxyl group of morphine. A chemical reaction is postulated to permit epibatidine to function as an analgesic. The carbon-chlorine bond should be activated by the neighbourhood of the nitrogen atom in the pyridine ring and therefore undergo a chemical reaction resulting in formation of a covalent bond, perhaps of an oxygen bridge between the opioid receptor and epibatidine.

Analgesics, Non-Narcotic↗
PubMed1993

A new consistent model explaining structure (conformation)-activity relationships of opiates with mu-selectivity.

Several different classes of opiates such as PET (7-alpha-(1-Hydroxy-1-methyl-3-phenylpropyl)-6,14-endo-ethenotetra - hydronorthebaine), phenazocine, fentanyl, carfentanil, ohmefentanyl, prodine derivatives, methadone and etonitazene have been investigated using the molecular modelling program package SYBYL and the TRIPOS empirical force field. Comparison of the energetically optimized structures and their corresponding molecular electrostatic potentials was used for the development of a new model of conformation-activity relationships of mu-selective opiates. We considered six important spatial positions of these molecules which were assumed to be directly implicated in the interaction with the opiate receptor. We found that these opiates may bind to the receptor with their protonated nitrogen atom assuming one or the other of two different orientations. The obtained results offer new insights into important receptor interactions and the diverse opiate activities of all the compounds examined can be explained in a unified manner. For example, the most active ohmefentanyl stereo-isomer was predicted on the basis of the proposed model.

Analgesics↗
PubMed1993

Classification of serine proteases derived from steric comparisons of their active sites.

The steric arrangements of the amino acyl residues in the catalytic triads and tetrads of the active site are compared with each other by means of systematic analysis of the conformation of the serine proteases stored in the Brookhaven Protein Data Bank. On this basis a differentiation between the representatives of the (chymo)trypsin family on the one hand and those of the subtilisin family on the other hand is found. The enzyme tonin distinguishes from representatives of the (chymo)trypsin family and should be classified to a new subclass of this family. Thermitase represents a new subclass of the subtilisins. The spatial orientation of the amino acyl residues of the active site of tonin suggests a new mechanism of enzyme catalysis that possibly also occurs in dipeptidyl peptidase IV.

Binding Sites↗
PubMed1992

The probable conformation of substrates recognized by dipeptidyl-peptidase IV and some aspects of the catalytic mechanism derived from theoretical investigations.

By theoretical conformational investigations of substrates and nonsubstrates of the enzyme dipeptidyl-peptidase IV (DP IV) as well as dipeptide-esters using the ECEPP83 method we determined the structure of peptides recognized and cleaved by the enzyme. From a comparison of all possible structures for the substrates with conformations not possible in nonsubstrates we concluded that a single conformation explains substrate specificities of DP IV. This conformation is characterized by the following dihedral angles: psi 1 = 85 degrees, omega 1 = 180 degrees, phi 2 = -75 degrees, psi 2 = 80 degrees, and omega 2 = 180 degrees. The conclusions were supported by comparisons of molecular electrostatic potentials calculated with the molecular graphics program HAMOG.

Amino Acid Sequence↗
PubMed1991

Conformational analysis of the tetrapeptide Pro-D-Phe-Pro-Gly in aqueous solution.

Conformational investigations of the tetrapeptide Pro-D-Phe-Pro-Gly in water solution were carried out by 1H and 13C NMR spectroscopy. The internal proline residue allows for the possibility of cis/trans isomerization about the D-Phe-Pro peptide bond resulting in two conformational isomers. The major isomer was identified as the trans isomer. The pH-dependence of the cis/trans equilibrium supports an additional stabilisation of the trans isomer by an intramolecular ionic interaction between the amino- and carboxy-terminus in the zwitterionic state. Based on 13C spin-lattice relaxation times (T1), different pyrrolidine ring conformations of Pro1 and Pro3 could be determined. By combination of several NMR data (vicinal coupling constants 3JN alpha, temperature dependence of the NH chemical shifts, differences in the chemical shifts between the beta and gamma carbons of the proline residues) and energy minimization calculations, a type II' beta-turn should contribute considerably to the overall structure of the trans isomer.

Endorphins↗
PubMed1991

HAMOG: molecular graphics program for chemistry, biochemistry, molecular biology and enzyme research.

HAMOG is a computer graphics program written in C for personal computers. Clear menus and a context-sensitive help option make the program easy to operate for occasional users. HAMOG provides a flexible environment for displaying and manipulating molecules and molecular systems. Special functions allow the investigation of structure-activity relationships of biologically active molecules. These include the calculation of molecular electrostatic potentials and fields, the superposition of molecules and the calculation of steric accessibilities. The visualization and manipulation of protein structures immediately readable from the Brookhaven Protein Data Bank files are also possible using HAMOG. The construction of any peptide or protein structure is very simple.

Chemical Phenomena↗
PubMed1990

[Effect of an angiogenesis-promoting dipeptide on microcirculation in experimental chronic stomach ulcer in the rat].

The influence of an angiogenesis stimulating dipeptide (Lys-Pro-derivative) on the blood flow rate of the stomach was tested in rats suffering from ulcus ventriculi by microspheres technique. 21 days after operation (acetic acid model by Takagi) the ulcers in the group treated with the dipeptide were healed completely, but not in the control group. The higher blood flow in the ulcer area of the dipeptide group radiometrically gained, was not changed significantly (U-test by Man-Whitney). These results demonstrate, that the process of rapid wound healing promoted by the dipeptide cannot entirely be explained by a higher blood flow of the stomach.

Angiogenesis Inducing Agents↗
PubMed1989

[Experimental chronic stomach ulcer].

A survey of different methods for the production of experimental gastric ulcer in rats is given. 20 male Wistarrats got a chronic gastric ulcer after the injection of 0.05 ml acetic acid (30%) under the serosa. We documented the developing of the ulcer in phases by means of histology. In contrast to other models the Acetic Acid Injection Ulcer (by Takagi et al. 1969) shows similar histology and chronicity to human histology and chronicity.

Acetates↗
PubMed1988

Properties of the transferrin associated with rat intestinal mucosa.

The transferrin that is isolated from washed intestinal mucosal cell preparations consists partly of a fraction that has properties distinguishing it from serum transferrin. The serum transferrin contaminating mucosal preparations, even when fully saturated with iron and in the presence of proteinase inhibitors, also acquires the properties of the mucosal transferrin when the mucosa is homogenised. The mucosal transferrin is modified by a single cleavage of the polypeptide chain yielding a disulphide-linked peptide of 6550 daltons linked to the parent protein by a disulphide bridge. The amino-terminal sequence of the first 11 residues of this peptide could be aligned with both the known rat and human transferrin carboxy-terminal sequences. In both cases the sequence is preceded by a phenylalanine residue (residue 622 of human transferrin). This suggested that a mucosal chymotryptic enzyme was responsible even though rat transferrin is not susceptible to alpha-chymotrypsin if fully iron-saturated. Since transferrin mRNA is not found in the intestinal mucosa it must be imported from the serum. It remains uncertain whether the modified transferrin is present naturally and plays a role in iron absorption but these findings do indicate the eventual fate of any transferrin imported into an intestinal cell.

Amino Acid Sequence↗
PubMed1988

Evidence for the involvement of protein-carbohydrate interaction in hematopoietic, multipotential colony-stimulating factor-dependent stem cell proliferation.

Immunologically important mediators have been shown to exhibit ability to specifically bind distinct carbohydrates. This type of protein-carbohydrate interaction is one mechanism how to explain involvement of glycochemical interactions in regulatory processes. Interference of certain saccharides with murine multipotential colony-stimulating factor (multi-CSF)-dependent colony formation from progenitor cells in semisolid agar raised evidence for similar potential involvement of protein-carbohydrate interactions. Affinity depletion of conditioned WEHI-3B-medium on resins, bearing saccharides that have been elucidated to be effective inhibitors (mannose and lactose), resulted in preparations with significantly reduced capability to sustain development and proliferation. Sequence comparison of multi-CSF to carbohydrate-binding proteins (lectins) with this specificity failed to uncover extended homologies in diagonal plots. But detailed sequence alignments revealed confined, high-scoring stretches of homology between various lectins and two types of CSF. These results prove the importance of protein-carbohydrate interactions in stem cell proliferation.

Amino Acid Sequence↗
PubMed1987

Cleavage of fibrin-derived D-dimer into monomers by endopeptidase from puff adder venom (Bitis arietans) acting at cross-linked sites of the gamma-chain. Sequence of carboxy-terminal cyanogen bromide gamma-chain fragments.

Puff adder venom contains a protease capable of cleaving the gamma-chain of cross-linked D-dimer, derived from the plasmin digestion of fibrin, into apparently symmetrical monomers. The cross-linked gamma-chains are separated in the process without apparent loss of mass and without loss of the substituent at the glutamine cross-link site, if fluorescent D-dimer (the lysine analogue dansylcadaverine used as substituent) is used as substrate [Purves, L. R., Purves, M., Lindsey, G. G., & Linton, N. J. (1986) S. Afr. J. Sci. 82, 30]. The gamma-chain from puff adder venom digested D-monomer was isolated and cleaved by cyanogen bromide, and the carboxy-terminal peptide was isolated and sequenced. The carboxy-terminal peptide composition indicated a lower content of histidine, leucine, and glycine than expected. Manual microsequencing by gas-phase Edman degradation demonstrated that two amino-terminal ends were present. By use of the known sequence of the human fibrinogen gamma-chain, the sequencing data could be resolved into a dipeptide cross-linked between lysine-406 and either glutamine-398 or -399 (residues 6 and 13 or 14 from the carboxy-terminal end of the gamma-chain) with the loss of residues 401-404 that occur between the cross-link sites of both antiparallel cross-linked gamma-chains. D-dimer is therefore separated into monomers by cleavage of the gamma-chain between the cross-link sites. Two symmetrical fragments are produced consisting of a cross-linked dipeptide with the loss of four amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1986

The delineation of a decapeptide gonadotropin-releasing sequence in the carboxyl-terminal extension of the human gonadotropin-releasing hormone precursor.

The human gonadotropin-releasing hormone (GnRH) precursor consists of the GnRH sequence followed by a 59-amino acid carboxyl-terminal extension. A 56-amino acid peptide within this extension has been shown to stimulate gonadotropin release, and this activity has been localized to its amino-terminal region. A series of seven overlapping peptide fragments corresponding to the first 24 amino acids of the carboxyl-extension of the GnRH precursor were synthesized and tested for their ability to stimulate luteinizing hormone and follicle-stimulating hormone release from cultured human anterior pituitary cells. All active peptide fragments were found to incorporate the decapeptide sequence Asn-Leu-Ile-Asp-Ser-Phe-Gln-Glu-Ile-Val which is regarded as a minimal structural requirement delineated for gonadotropin-releasing activity. A further flanking sequence extending this active region from its carboxyl terminus was found to enhance gonadotropin-releasing activity although the flanking sequence itself was inactive. The gonadotropin release stimulated by the active peptides wa shown to be a dose- dependent, specific, and calcium-dependent phenomenon which occurred independently of the GnRH receptor on the pituitary gonadotrophs as a GnRH antagonist did not inhibit activity.

Adolescent↗