Biomedical subjects

P Ertl

Publications and source records attributed to P Ertl.

22 records · Page 2Linked to original sources

PubMed1988

Synthesis and activity of partial retro-inverso modified atrial natriuretic factor analogs.

The synthesis and pharmacological activity of partial retro-inverso modified rat atrial natriuretic factor (rANF) analogs is described. The route to these compounds utilized a combination of solution and solid-phase methods. The analogs prepared all contain a reversed amide bond (psi[NHCO]) at the Ser 25 to Phe26 linkage. This bond has been suggested to play a key role in the metabolic inactivation of ANF. The analogs are of comparable potency to the endogenous peptide rANF1-28 in binding to cultured rat vascular smooth muscle cells, in relaxing serotonin contracted rabbit aortic rings, and as natriuretic/diuretic agents in anesthetized rats. None of the peptides has an extended duration of action in vivo.

Animals↗

PubMed1988

Characterization of human immunodeficiency virus type 1 reverse transcriptase by using monoclonal antibodies: role of the C terminus in antibody reactivity and enzyme function.

We describe the production of eight monoclonal antibodies reactive with human immunodeficiency virus type 1 reverse transcriptase (RT) by immunization of mice with purified recombinant RT. These antibodies were found to react with one or the other of two regions of the enzyme and were found to be useful in immunodeficiency purification of large amounts of the enzyme. One epitope located at the C terminus of the enzyme was of particular interest, since it was present in only the larger, 66-kilodalton (kDa) RT species and not its smaller, 51-kDa counterpart. To define this epitope, a series of mutants was made which synthesized C-terminally truncated RT. These mutants indicated that the same region of the enzyme, when deleted, both removed the C-terminal epitope and drastically reduced RT activity, indicating the importance of this region in the function of the enzyme; however, even the 51-kDa enzyme component had demonstrable activity.

Animals↗

PubMedDate not supplied

Computational modeling of a binding conformation of the intermediate L-histidinal to histidinol dehydrogenase.

Histidinol dehydrogenase (HDH) is one of the enzymes involved in the L-histidine biosynthesis pathway. HDH is a dimer that contains one Zn2+ ion in each identical subunit. In this study, we predicted a possible binding conformation of the intermediate L-histidinal, which is experimentally not known, using a computational modeling method and three potent HDH inhibitors whose structures are similar to that of L-histidinal. At first, a set of the most probable active conformations of the potent inhibitors was determined using two different pharmacophore mapping techniques, the active analogue approach and the distance comparison method. From the most probable active conformations of the three potent inhibitors, the common parts of the L-histidinal structure were extracted and refined by energy minimization to obtain the binding conformation of L-histidinal. This predicted conformation of L-histidinal agrees with an experimentally determined conformation of L-histidine in a single crystal, suggesting that it is an experimentally acceptable conformation. The capability in this conformation to coordinate a Zn2+ ion was examined by comparing the spatial relative geometry of its functional groups with those of ligands that coordinate with a Zn2+ ion in Zn proteins of the Protein Data Bank. This comparison supported our predicted conformation.

Alcohol Oxidoreductases↗

PubMedDate not supplied

Web-based cheminformatics and molecular property prediction tools supporting drug design and development at Novartis.

Web-based tools offer many advantages for processing chemical information, most notably ease of use and high interactivity. Therefore more and more pharmaceutical companies are using web technology to deliver sophisticated molecular processing tools directly to the desks of their chemists, to assist them in the process of designing and developing new drugs. In this paper, the web-based cheminformatics system developed at Novartis and currently used by more than thousand users is described. The system allows various molecular modeling and molecular processing tasks, including the calculation of molecular and substituent properties, property-based virtual screening, visualization of molecules, bioisosteric design, diversity analysis, and support of combinatorial chemistry. The methodology to calculate various molecular properties relevant to drug design is described, including the prediction of intestinal absorption, blood-brain barrier penetration, efflux, and water solubility. Information about the web technology used is also provided.

Drug Design↗