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Design and characterization of bioactive hybrid peptides for therapeutic application and functionalization with nanoparticles

Abstract

It is well known that many multicellular organisms produce a variety of peptides, namely host defense peptides and antimicrobial peptides (AMPs), which are effective defensive weapons against a wide range of pathogens including, bacteria, fungi, enveloped viruses, protozoa, as well cancer cells. Due to their versatility and unlimited sequence space, the AMPs can be rationally designed by modulating physicochemical determinants to favor desired biological parameters and turned into novel therapeutics. In this project, we propose use key structural and physicochemical parameters, in combination with rational engineering on bioinformatic tools, to design peptides from toxins and novel hybrid structures inspired by the well-known natural peptides. We will investigate important characteristics such as the composition of amino acids, secondary structures, liquid charges, amphypathicity, antimicrobial and antitumor activity. Alternative models such as Galleria mellonella and Danio rerio (zebrafish) will be used to evaluate peptide toxicity, presenting a reliable invertebrate and vertebrate model to determine, developmental toxicity, general toxicity and to perform an initial drug screening. Biophysical studies on cell membranes and model membranes that have been widely used are proposed in the project, which can infer information about the action of peptides on the electrostatic and elastic characteristics of the membrane. It is expected that the peptides created exhibit physicochemical characteristics required for their pharmacological activity and low toxicity. Lastly, we intend to functionalize nanoparticles (NPs) with selected hybrid peptides. The peptides designed and their functionalization with nanoparticles are expected to overcome the pharmacokinetic problems of the peptides and promote their prolonged. The challenge of peptide functionalization with nanoparticles can enhance the therapeutic efficiency of the peptides through targeted delivery, as well as the synergistic effect of the NP-peptide. This study can reveal the therapeutic potency of a novel hybrid peptides (prototype compound) and supports the use of rational design in development of new peptide drugs. (AU)

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