The development of a holistic and effective strategy for the control of cell proliferation, and perhaps malignancy expression, depends on the knowledge of the targets of inhibitors of cell growth and their different mechanisms of action. Polyamines play a vital role in prokaryotic and eukaryotic cell growth and differentiation. A compound(s) produced by Pseudomonas cepacia and Bacillus thuringiensis, which inhibit the growth of the fungus Macrophomina phaseolina, may also inhibit methionine and polyamine biosynthesis.
The specific aims of the proposed study are: to purify and characterize the inhibitor(s) produced by Pseudomonas and Bacillus, and to determine the presence of this inhibitor(s) in other bacteria; to determine the enzymatic mechanism by which Macrophomina is inhibited by this compound(s); to examine to what extent this compound(s) inhibits the growth of other cell types; and to determine the relationship between cell growth inhibition by this compound(s) and polyamine biosynthesis. The inhibitor will be purified by ion exchange and high pressure liquid chromatography, and characterized by elemental analysis, an ultraviolet, infrared, nuclear magnetic resonance, and mass spectroscopies. In vitro susceptibility tests, polyamine content determination, and biochemical target determination experiments will be performed. Purification and kinetic characterization, and inhibition studies of the enzymes involved, beta-cystathionase and polyamine biosynthesis enzymes, will follow. Our long term goal is to determine the role, at the molecular level, of this inhibitor(s) in the control of cell growth and differentiation. With this knowledge effective chemotherapeutic strategies can be designed, using selective agents which can penetrate the cell and specifically inhibit essential reactions.

Project Start
Project End
Budget Start
Budget End
Support Year
22
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Puerto Rico Mayaguez
Department
Type
DUNS #
City
Mayaguez
State
PR
Country
United States
Zip Code
00681
Díaz Casas, Adalberto; Chazin, Walter J; Pastrana-Ríos, Belinda (2017) Prp40 Homolog A Is a Novel Centrin Target. Biophys J 112:2529-2539
Lara Rodriguez, L; Sundaram, P A (2016) Corrosion behavior of plasma electrolytically oxidized gamma titanium aluminide alloy in simulated body fluid. Mater Chem Phys 181:67-77
Bueno-Vera, J A; Torres-Zapata, I; Sundaram, P A et al. (2015) Electrochemical characterization of MC3T3-E1 cells cultured on ?TiAl and Ti-6Al-4V alloys. Bioelectrochemistry 106:316-27
Pastrana-Rios, Belinda; Del Valle Sosa, Liliana; Santiago, Jorge (2015) Trifluoroacetic acid as excipient destabilizes melittin causing the selective aggregation of melittin within the centrin-melittin-trifluoroacetic acid complex. Struct Dyn 2:041711
Santiago-Medina, P; Sundaram, P A; Diffoot-Carlo, N (2015) Titanium Oxide: A Bioactive Factor in Osteoblast Differentiation. Int J Dent 2015:357653
Santiago-Medina, Pricilla; Sundaram, Paul A; Diffoot-Carlo, Nanette (2014) The effects of micro arc oxidation of gamma titanium aluminide surfaces on osteoblast adhesion and differentiation. J Mater Sci Mater Med 25:1577-87
Vera, José L; Rullán, Jorge; Santos, Natasha et al. (2014) Functionalized ferrocenes: The role of the para substituent on the phenoxy pendant group. J Organomet Chem 749:204-214
Lara Rodriguez, L; Sundaram, P A; Rosim-Fachini, E et al. (2014) Plasma electrolytic oxidation coatings on ?TiAl alloy for potential biomedical applications. J Biomed Mater Res B Appl Biomater 102:988-1001
Dominguez-Garcia, Moralba; Ortega-Zuniga, Carlos; Melendez, Enrique (2013) New tungstenocenes containing 3-hydroxy-4-pyrone ligands: antiproliferative activity on HT-29 and MCF-7 cell lines and binding to human serum albumin studied by fluorescence spectroscopy and molecular modeling methods. J Biol Inorg Chem 18:195-209
Pastrana-Rios, Belinda; Reyes, Myrna; De Orbeta, Jessica et al. (2013) Relative stability of human centrins and its relationship to calcium binding. Biochemistry 52:1236-48

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