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Updated: Feb 1, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
Structure-function-guided exploration of the antimicrobial peptide polybia-CP identifies activity determinants and
Marcelo D T Torres1,2,3, Cibele N Pedron3, Yasutomi Higashikuni1,2
11Synthetic Biology Group, MIT Synthetic Biology Center; The Center for Microbiome Informatics and Therapeutics; Research Laboratory of Electronics, Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139 USA.
Abstract:
Antimicrobial peptides (AMPs) constitute promising alternatives to classical antibiotics for the treatment of drug-resistant infections, which are a rapidly emerging global health challenge. However, our understanding of the structure-function relationships of AMPs is limited, and we are just beginning to rationally engineer peptides in order to develop them as therapeutics. Here, we leverage a physicochemical-guided peptide design strategy to identify specific functional hotspots in the wasp-derived AMP polybia-CP and turn this toxic peptide into a viable antimicrobial. Helical fraction, hydrophobicity, and hydrophobic moment are identified as key structural and physicochemical determinants of antimicrobial activity, utilized in combination with rational engineering to generate synthetic AMPs with therapeutic activity in a mouse model. We demonstrate that, by tuning these physicochemical parameters, it is possible to design nontoxic synthetic peptides with enhanced sub-micromolar antimicrobial potency in vitro and anti-infective activity in vivo. We present a physicochemical-guided rational design strategy to generate peptide antibiotics.
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