In recent years, many pathogenic organisms have developed resistance to traditional drugs. This situation has forced researchers to look for new active antibiotics by modification of current drugs, design new drugs or the search of novel active compounds from natural sources.
Venoms are a rich source of biologically active molecules. Venomous animals, plants and microbes have evolved to produce an array of toxins as a defensive or an offensive strategy to attack and capture prey. From animals alone, about 2500 compounds are known that are believed to act as defense mechanisms.
Antimicrobial peptides (APs) are of current interest as potential drugs for the treatment of infectious diseases. Unlike small molecules that usually act against a specific macromolecular target, most APs act through a biophysical mechanism, exhibiting their antimicrobial activity by binding to the bacterial cell membrane and disrupting its structure. Because of this general mode of action, there are few mechanisms of resistance that microbes have developed against antimicrobial peptides. This is a major potential advantage of this type of antibiotic, over active site-directed antibiotics, such as beta-lactams.
My research consists in the synthesis of short peptides derived from natural peptides found in scorpion venoms with antibiotic activity. In order to avoid protease cleavage and modulate activity, modifications are introduced in the form of fluorinated residues.
In collaboration with the Department of Biology synthetic peptides are tested in vivo for their antibiotic activity.
Gottler, L; de la Salud-Bea, R; Shelburne, C; Ramamoorthy, A; Marsh, E.N.;
“Using Fluorous Amino Acids to Probe the Effects of Changing Hydrophobicity
on the Physical and Biological Properties of the beta-Hairpin Antimicrobial Peptide
Protegrin-1.” Biochemistry 2008, 47, 9243-9250
Berkowitz, D.; Karukurichi, K.; de la Salud-Bea, R.; Nelson, D.; McCune, C.;
“Use of Fluorinated Funtionality in Enzyme Inhibitor Development: Mechanistic
and Analytical Advantages.” Journal of Fluorine Chemistry 2008, 129, 731-742.
Gottler, L.; de la Salud-Bea, R.; Marsh, E.N.; “The Fluorous Effect in Proteins:
Properties of a4F6, a 4-alpha-Helix Bundle Protein with Fluorocarbon Core.”
Biochemistry 2008, 47, 4484-4490
Karukurichi, K.; de la Salud-Bea, R.; Jahng,W.J.; Berkowitz, D. “Examination of
the New alpha-(2’Z-Fluoro)vinyl Trigger with Lysine Decarboxylase: The Absolute
Stereochemistry Dictates the Reaction Course.” J. Am. Chem. Soc. 2007, 129,
Berkowitz, D.; de la Salud-Bea, R.; Jahng, W.J. “Synthesis of Quaternary Amino
Acids Bearing an alpha-(2’Z-Fluoro)vinyl Branch: Potential PLP Enzyme
Inactivators.” Organic Letters 2004, 6, 1821-1824.
Ph.D. University of Nebraska-Lincoln (Chemistry)
M. A. University of Valencia (Spain) (Chemistry)
B.S. University of Valencia (Spain) (Chemistry)