In my lab, I have two projects that combine synthetic methodology and biological activity of novel compounds.
Project 1: Synthesis of peptides and their testing for toxicity, antimicrobial, anticancer and insecticide properties.
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.
In this project we design and synthesize short peptides (analogs) derived from natural peptides found in animal venoms (scorpions, wasps and currently fishes) with antibiotic activity. Because of their intrinsic toxicity and to, potentially increase their antimicrobial activity, specific modifications are done in their primary structure by replacing amino acids or the length of the sequence.
In collaboration with the Department of Biology, synthetic peptides are tested in vivo for their biological activities.
Project 2: Synthesis of unnatural amino acids.
Since the number of natural amino acids is limited, in our lab we have designed a number different side chains that produce amino acids with new properties ranging from vey hydrophobic to ionic. Our goal is to build a library of different amino acids to be incorporated in the design of new peptides for our project 1.
These two projects have attracted the interest of not only Chemistry majors but also students in Biology and in Biology and Molecular Biology majors as part of their experience in a research group.
I also serve as the Radiation Safety Officer for MAX.
Publications. (All published articles are peer-reviewed)
De la Salud Bea R., Frawley, E.R., Shen, Q., Moyo, S., Thelven, J., North, L.J.; “Synthesized peptide analogs from Eumenes pomiformis (Hymenoptera: Eumenidae) venom reveals their antibiotic and pesticide activity potential” Toxicon, 2023, 224, 1
De la Salud Bea R., North, L.J., Horiuchi, S., Frawley, E.R., Shen, q.; “Antimicrobial Activity and Toxicity of Analogs of Wasp Venom EMP Peptides. Potential Influence of Oxidized Methionine” Antibiotics, 2021, 10, 1208
De La Salud Bea R., Petraglia, A.F., Ascuitto M.R. Buck, Q.M.; “Antibacterial Activity and Toxicity of Analogs of Scorpion Venom IsCT Peptides” Antibiotics, 2017, 6, 13
McCune, C., Beio, M., Sturdivant, Jill; de la Salud-Bea, Roberto; Darnell, Brendan; Berkowitz, David.; “Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1’-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators.” Journal of the American Chemical Society 2017, 139, 14077
De La Salud Bea, R., Petraglia, A.F., de Johnson, L.E.L.; “Synthesis, Antimicrobial Activity and Toxicity of Analogs of the Scorpion Venom BmKn Peptides.” Toxicon. 2015, 101, 79-84.
De la Salud Bea, R., Ascuitto, M.R., de Johnson, L.E.L.; “Synthesis of Analogs of Peptides from Buthus martensii Scorpion Venom with Potential Antibiotic Activity.” Peptides. 2015, 68, 228-232
Brender, J. R., Hartman, K.; Nanga, R.P.K., Popovych, N., de la Salud Bea, R., Vivekanandan, S., Marsh, E. Neil G.; Ramamoorthy, A.; “Role of Zinc in Human Islet Amyloid Polypeptide Aggregation.” Journal of the American Chemical Society 2010,132, 8973-8983
Buer, B.; de la Salud-Bea, R.; Hasim, M.A.; Marsh, E.N.; “Engineering Protein Stability and Specificity Using Fluorous Amino Acids: The importance of Packing Effects.” Biochemistry 2009, 48, 10810-10817
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 b-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-a-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 a-(2’Z-Fluoro)vinyl Trigger with Lysine Decarboxylase: The Absolute Stereochemistry Dictates the Reaction Course.” Journal of the American Chemical Society. 2007, 129, 258-259
