Scientists are using a pioneering approach called structure-guided design to develop powerful new antibiotic candidates. This complex process allows for highly accurate modifications to the chemical structure of these peptides. It’s at the forefront of the battle against deadly antibiotic-resistant bacteria. Cesar de la Fuente’s lab at the University of Pennsylvania is focused on this groundbreaking research. Right now, they’re most interested in improving the delivery, function and antimicrobial activity of these peptides. The team is currently implementing the alternative design of synthetic peptides by changing the molecular sequence. This approach holds great potential for producing a steady stream of new antibiotic winners.
Advancements in Structure-Guided Design
Structure-guided design is a highly technical and highly creative process used to sculpt chemical structure into desirable molecules. Through careful manipulation of the arrangement of a molecule’s parts, scientists can improve upon its natural characteristics and effectiveness. This approach is being employed in the development of synthetic peptides, a new class of antibiotics. Compared to writing random libraries of peptides, structure-guided design enables scientists to modify unmodified peptides to produce several antibiotic candidates without the limitations of unmodified peptides.
"With structure-guided design, we change the sequence of the molecule," explained Marcelo Torres, a key contributor to the research.
The verification process requires painstaking testing of synthetic, peptide-based antibiotics against dozens of harmful bacteria. Nonetheless, orchestrating these experiments is a major hurdle because it involves the concurrent cultivation of multiple bacterial strains. The iterative, experimental design process remains a key element of de la Fuente’s lab. It fuels the continuing research, despite the adversity.
Harnessing Nature for Medical Innovation
Cesar de la Fuente, Presidential Associate Professor, Bioengineering and Chemical and Biomolecular Engineering As we dive into the creation of new antibiotic molecules, he points out that nature plays an integral role in that inspiration. His lab is looking at the secretions of frogs endemic to South Asia to create synthetic peptides from these amphibians with stronger antimicrobial properties. This strategy would further complement de la Fuente’s idea of using natural resources to fuel biomedical progress.
"We are excited that frogs—and nature in general—can inspire new molecules that could be developed into antibiotics," de la Fuente shared.
Her group’s newfound control over natural molecules to create more valuable, next-generation antibiotics exemplifies the promise of engineering to the development of new drugs. Structure-guided design continues to lead this transformative movement. Most notably, it accelerates the development of novel synthetic peptides specifically tailored to fight key bacterial threats.
"Thanks to the power of engineering, we can take those natural molecules and turn them into something more useful for humanity," he added.
Challenges and Future Prospects
Though there is great potential in applying structure-guided design, the road to creating new antibiotics is not an easy one. Laboratory experimentation needs careful conditions and controlled study with rigorous testing across spectrum of bacteria. Thanks to the groundbreaking approach taken by de la Fuente’s team, new methods are leading to breakthroughs in antibiotic research.
"Each study is motivated by imagining environments where evolution would spur the creation of antibiotics," remarked de la Fuente.
By zeroing in on evolutionary processes and natural sources, the researchers hope to develop antibiotics that are effective in fighting disease but sustainable. Progress in eradicating antibiotic resistance is in part thanks to the work of De la Fuente’s lab. We’re proud to support their continuing work to address this global challenge.