UP Scientists Explore Alanine’s Effect on Spider Venom Antimicrobial Peptide

By Eunice Jean C. Patron

Antimicrobial resistance is a global issue, making the search for a new generation of antibiotics imperative. Scientists investigate various compounds to discover new antibiotics, one class of which is antimicrobial peptides (AMPs), produced by organisms in response to bacterial infections.

Commercially available AMPs are still a long way off, but research on their structure and antimicrobial activity is ongoing, since scientists believe that bacteria develop resistance to AMPs more slowly. Existing studies show that animal venoms are known to be rich sources of molecules with potential pharmacological applications, prompting researchers to investigate their antimicrobial properties.

Jomari Fernando and Dr. Aaron Joseph Villaraza of the UP Diliman College of Science’s Institute of Chemistry (UPD-CS IC), along with Jeremiah Batucan, Jacquelyn Peran, and Dr. Lilibeth Salvador-Reyes of the UPD-CS Marine Science Institute (MSI), examined how replacing certain amino acids with alanine—an amino acid involved in protein formation—affected the structure and antimicrobial activity of lyp1987, an AMP derived from the venom of the wolf spider Lycosa poonaensis.

Their findings show that, while the minor changes they applied on the compound had no pronounced effect on its structure, there were major effects on its antimicrobial activity. By replacing amino acids Glu12 and Thr17 with alanine, lyp1987’s antibacterial activity against both Gram-positive and Gram-negative bacteria improved. Substituting amino acid Lys9 with alanine also made the wolf spider’s AMP target Gram-positive bacteria more specifically.

Fernando expressed his surprise by the AMP’s effect on the human cells he obtained from the bioactivity experiments. “I observed that as my compounds had higher antimicrobial activity, there was also an increase in their toxicity against human cells. Some modifications on the native peptide also made it prefer to kill a particular bacteria over the other,” he explained.

“We were able to synthesize the compound and its analogs in the laboratory in their pure form and test their antimicrobial property and probable toxic effects on human cells with the help of the group of MSI,” he added, mentioning that although they are not continuing this study or researching AMPs in general, their work provides a working pipeline for studying the structure and antimicrobial activity of both known and yet-to-be-discovered AMPs.

Their research, titled “The Wheel of Fortune: Helical Wheel Alanine Scanning of a Spider Venom Antimicrobial Peptide Reveals Residues Involved in Antimicrobial and Cytotoxic Activity,” is featured in ChemMedChem, a journal that publishes high-impact articles showcasing the breadth of international research in medicinal chemistry, from small pharmacologically active molecules to new modalities including nanomedicine and biologics. This study was supported by the Royal Society of Chemistry Research Fund.

References:

Fernando, J. C., Batucan, J. D., Peran, J. E., Salvador‐Reyes, L. A., & Villaraza, A. J. (2024). The wheel of fortune: Helical wheel alanine scanning of a spider venom antimicrobial peptide reveals residues involved in antimicrobial and cytotoxic activity. ChemMedChem, 19(23). https://doi.org/10.1002/cmdc.202400488