Euro-Global Conference on Biotechnology and Bioengineering

September 06-08, 2021 | Online Event

September 06-08, 2021 | Online Event
ECBB 2021

Robert S. Hodges

Speaker at Biotechnology and Bioengineering 2021 - Robert S. Hodges
University Of Colorado, United States
Title : Next generation of de novo designed amphipathic ?-helical antimicrobial peptides to treat the gram-negative pathogen, Acinetobacter baumannii


There are now “Superbugs” that are resistant to all available antibiotics.  We have designed de novo and synthesized a series of 26-residue all D-conformation amphipathic α-helical cationic antimicrobial peptides (AMPs) to understand the role of the type of hydrophobe on the non-polar face (Ile, Leu and Nle), the type of positively charged residues on the polar face (Arg, Lys, Orn, Dab and Dap) and the incorporation of Dab and Dap residues on the polar face as L, D or combinations of L and D.  All these substitutions were tested against 7 strains of Acinetobacter baumannii resistant to antibiotics of last resort (colistin and polymyxin B) and 20 world-wide isolates from 2016 and 2017 with resistance to 18 different antibiotics.  These isolates came from 4 continents, 12 different countries, and 17 different cities. The two positively charged residues in the center of the non-polar face (Lys 13 and Lys 16) provide specificity for prokaryotic cells over eukaryotic cells, prevent unwanted high affinity binding to serum proteins as well as selectivity against gram-negative organisms.   Our AMPs have excellent antimicrobial activity and have no toxicity as measured by the most stringent test for hemolysis of human red blood cells (18 hours at 37oC and up to 1000 µg/ml of AMP).  This study clearly shows the potential of our AMPs with specificity determinants (Lys 13 and Lys 16) and the use of unusual amino acid residues (Dab and Dap) as polar face positively charged residues.  Our compounds have no stereochemical targets and thus the development of bacterial resistance is unlikely.  We will also discuss: 1) the successful pegylation of our AMPs; 2) toxicity against 4 primary human cell lines (hepatocytes, iPSC cardiomyocytes, renal proximal tubule cells and endothelial cells); and 3) in vivo toxicity of our lead AMPs.  Our results show that these compounds are the next generation of antimicrobials and will replace existing antibiotics as new therapeutics.

Presentation Learning Outcome

The audience will learn the process for de novo design of peptide therapeutics, the importance of perfecting the biological assays before implementing structure-function studies.  Just because an assay has been used for many years does not mean it should not be changed. If developing therapeutics for humans use a human source of materials for biological assays. For antimicrobial assays select the most recent bacterial strains that are resistant to key antibiotics and not a few standard strains. Though nature is restricted to using the amino acids Arg and Lys, a synthetic peptide approach has much more freedom with the use of unusual amino acids for positively charged amino acids e.g. Orn, Dab, and Dap. This presentation clearly shows that great discoveries are dependent on the details. Try to think outside of the box. In our case, the peptide length and the design of the template were critical in the final success of our research.


Dr. Hodges has been Professor of Biochemistry and Molecular Genetics and the John Stewart Chair in Peptide Chemistry at the University of Colorado, Anschutz Medical Campus, Aurora, CO, for the past 20 years.  He has a broad background in synthetic peptide chemistry having trained with Dr. Bruce Merrifield at Rockefeller University, a Nobel Laureate who developed solid-phase peptide chemistry.  Dr. Hodges has successfully used this technology to study the structure and function of peptides and proteins, the feasibility of developing antimicrobial peptides with specificity for Gram-negative pathogens to developing synthetic peptide vaccines to α-helical B-cell epitopes in Type 1 fusion proteins of emerging and re-emerging viruses.  He has won many awards.  He is a Fellow of the Royal Society of Canada, the Vincent Du Vigneaud Award from the American Peptide Society for outstanding achievements in peptide/protein research and most recently the Bruce Merrifield Award for outstanding lifetime accomplishment in peptide research recognizing the highest level of scientific creativity in 2017.