Multi-drug resistance pathogens are a serious health threat worldwide and there is an urgent need for the development of novel drugs to target these organisms. The variety of natural compounds still displays one of the largest resources for the discovery of novel pharmaceutical lead compounds. In particular peptides have recently attracted much interest in drug development approaches. This is in large part due to advances in analytical techniques to identify novel compounds and synthetic chemistry that is encouraging to overcome their major limitations such as poor stability and low oral bioavailability.
Antimicrobial peptides (AMP) are a large class of molecules known to play an important role in the innate immune system of many organisms, including insects. AMPs have been shown to be not only able to interact with biological membranes but have been equally ascribed to modulate immunity via intracellular targets. Their activity against a range of microorganisms, including relevant pathogens make them interesting molecules for the discovery of novel lead compounds. Although insects make up ~80% of all living species, little is known about the peptide content of individual species and their pharmacological potential.
In this study we aim to discover and characterize novel bioactive peptides, determine their three-dimensional structure and evaluate their pharmacological activity. Synthesis of optimized peptide compounds further aims to identify their molecular targets and determine their potential as novel drug leads. These goals will be accomplished by using a peptidomics workflow that combines state-of-the-art mass spectrometry analyses together with transcriptome mining. Solid-phase peptide synthesis will be used to obtain sufficient material for subsequent NMR structural and bioactivity studies.