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43 results on '"Gabriel, Jerome L."'

18. Common and specific determinants for fibroblast growth factors in the ectodomain of the receptor kinase complex

Author

Wang, Fen, Lu, Weiqin, McKeehan, Kerstin, Mohamedali, Khalid, Gabriel, Jerome L., Kan, Mikio, and McKeehan, Wallace L.

Subjects
Fibroblast growth factors -- Research, Protein kinases -- Research, Cellular signal transduction -- Research, Biological sciences, Chemistry
Abstract

Research was conducted to define the relative role of each of the two immunoglobulin (Ig)-like modules and flanking sequences in the common and specific binding of FGF-1, FGF-2 and FGF-7. Functional analysis and site-directed mutagenesis revealed three sites that contribute to the absolute rejection of FGF-7 by FGFR1IIIc. Results provide evidence that a complex of Ig module II and heparan sulfate is the base common core of the FGFR ectodomain.

Published
1999

35. Quantitative StructureActivity Relationships of Perfluorinated HeteroHydrocarbons as Potential Respiratory Media

Author

Gabriel, Jerome L., Miller, T. F., Wolfson, Marla R., and Shaffer, Thomas H.

Abstract

It has been extensively reported that liquidassisted ventilation, using inert perfluorocarbon liquids PFCs, can reduce interfacial surface tension and allow for improved ventilation at decreased alveolar pressures. PFCs are bioinert, minimally absorbed, and have no deleterious histologic, cellular, or biochemical effects when used as respiratory media. Although several types of PFCs have been characterized, a select few are considered to be compatible with life. Compatibility is often related to the physicochemical profile inherent to the PFC liquids. It is essential that certain physical properties such as respiratory gas solubility, vapor pressure, density, viscosity, and tissue permeability be within a narrow, acceptable range for a PFC to be considered as a possible candidate for respiratory media. The current study sought to characterize the physicochemical profile of commercially available PFCs. This was accomplished by creating a method for accurate, rapid prediction of a host of unknown physical characteristics of PFCs. The physicochemical properties of 16 perfluorinated heterohydrocarbons were catalogued from the literature. The input data were categorized into three major groups empiric properties, geometric indices, and quantum mechanical descriptors, to generate a database. Algorithms were then developed, one for each dependent variable FUNCTION, including oxygen solubility, partition coefficient logP, vapor pressure, viscosity, and density, that related the values of these physical properties of potential breathable PFC liquids to the parameters listed in the database. The general form of the algorithm can be written as follows FUNCTION CiPiPiconstant where the FUNCTIONS are oxygen solubility, logP, vapor pressure, viscosity, and density. Ciis a coefficient that weights the relative contribution of each parameter. Each independent parameter, Pi, was normalized by the average value of the parameter used in the analysis, Pi. Residual analysis demonstrated validity with all five equations. This method is expected to assist in the prediction of physical properties of PFC liquids with acceptable accuracy, such that PFC production and selection from currently available liquids can be optimized for each liquid ventilation application.ASAIO Journal199642968973.

Published
1996

36. Alteration in the Retinoid Specificity of Retinoic Acid Receptor-β by Site-directed Mutagenesis of Arg269and Lys220(∗)

Author

Tairis, Nikolaos, Gabriel, Jerome L., Soprano, Kenneth J., and Soprano, Dianne Robert

Abstract

Retinoic acid receptor-β (RAR-β) specifically binds retinoic acid (RA) and functions as a RA-inducible transcriptional regulatory factor. Simultaneous mutation of Arg269and Lys220of RAR-β to Ala results in a dramatic reduction in both transactivation and affinity for RA along with creating a RA concentration-dependent dominant negative mutant. In this report, we found that mutation of these two amino acid residues singly and simultaneously to Gln results in mutant RAR-βs, each displaying a more dramatic reduction in transactivation and affinity for RA than their corresponding Ala mutant, with the R269Q more profoundly affected than K220Q. Furthermore, we examined both the Ala and Gln mutants for their ability to transactivate and bind two other retinoids with different functional end groups (all-trans-retinol and all-trans-retinal). Mutation of Lys220to either an Ala or a Gln favors transactivation and binding of retinal, while mutation of either Lys220or Arg269to Gln favors retinol transactivation and binding. Taken together, these results suggest that Arg269and Lys220lie within the ligand binding pocket of RAR-β and that these two amino acid residues play an important role in determining retinoid specificity most likely by directly interacting with the carboxylate group of RA.

Published
1995
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43. Ether and Carbamate Derivatives of 3-quinuclidinol and 3- hydroxymethylquinuclidine: Synthesis and Evaluation as Nicotinic Ligands.

Author

Annadurai S, Zhang M, Gabriel JL, Bencheriff M, and Canney DJ

Subjects
Acetylcholine metabolism, Animals, Carbamates chemical synthesis, Drug Partial Agonism, Ethers chemical synthesis, Female, Humans, Ligands, Models, Molecular, Neurotransmitter Agents metabolism, Nicotinic Agonists chemical synthesis, PC12 Cells, Quinuclidines chemical synthesis, Rats, Rats, Sprague-Dawley, Synaptosomes metabolism, Carbamates pharmacology, Ethers pharmacology, Nicotinic Agonists pharmacology, Quinuclidines pharmacology
Abstract

Background: A lead quinuclidine-based nicotinic ligand (EQA) served as the basis for the design of novel compounds. A new series of 3-substituted quinuclidines was designed, synthesized and evaluated as nicotinic ligands., Methods: The goal was to improve affinity for nicotinic receptors in the CNS. Interatomic distance calculations were performed on the proposed compounds as well as, known nicotinic ligands. The proposed compounds were then synthesized, characterized and evaluated in in vitro assays as nicotinic receptor ligands., Results: Compounds 9a and 9b were found to inhibit the specific binding of 3H-(S)-Nicotine with Ki values of 48 nM and 42 nM respectively, indicating high affinity interactions with the α4β2 subtype. Data suggest that several compounds act as partial agonists at CNS receptors with an efficacy between 28 and 40% and are potent partial activators of human muscle type receptors (α1β1γδ Emax= 80% that of 100 µM nicotine)., Conclusions: Together these results indicate a partial agonism at muscle type receptors (ca. 40%) with no significant activation of rat ganglion-type receptors (α3β4*: asterisk indicates potential additional subunit that could partner to form the ganglionic receptor). The partial agonism inducing dopamine release from striatal synaptosomes (α4β2α6α4β2β3, and/or α6β2β3) suggest that these compounds may in addition be acting at the α4β2 and/or the α6β3* receptors. The partial agonists reported herein are interesting nicotinic ligands worthy of further investigation.

Published
2016
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