Our proposed research consists of three work packages (WPs). In WP1, we plan to design and prepare three kinds of PEP-POMs by covalent modification or noncovalent self-assembly. Next, the photothermal capacity of these PEP-POMs will be comprehensively studied in WP2. Finally, in WP3, we are going to evaluate their antimicrobial performance on antibiotic-resistant bacteria, and we will also investigate the possibility for the emergence of their resistance induced by photothermal therapy.
During our project, we designed two man-made nanosized amino acid (POM amino acid, including POM as pendant R group and POM as main chain amino acid) for robotic synthesis of giant anionic peptides by a common peptide synthesizer. 1) This is the first time that hybrid organic-inorganic amino acid can be robotically incorporated into giant anionic peptides. By using the above technique, the preparation of POM-peptides becomes controllable, robotic and automatic in peptide synthesizer. We demonstrated four POM-peptides with POM at C-terminal, N-terminal and middle part, respectively. 2) Moreover, we also demonstrate the tolerance of Fmoc POM amino acid to all kinds of amino acid containing hydrophilic, aromatic, alkyl chain, positively charge and negatively charge. This breakthrough is the key to broaden the application scope for POM amino acid in de novo design of functional anionic peptides.3) This work provides a facile and robotic approach to prepare giant anionic peptides with precise control of anion numbers and size in a wide range. In the following research work, we are going to investigate the bonding interaction between these POM-peptide towards certain protein, we believe this work provide a method to deeply investigate the relationship between sequence of POM peptide with their biological performance.
During this period, we found another interesting project. Modulating complex nanostructures under precise control is critical yet challenging. Polyoxometalates (POMs) have made remarkable progress since a series of compounds, show promising antitumor, antiviral, and antibacterial effects however their function is closely related to their self-assembled structure which is challenging to synthetically control. In this work we have utilized five oligopeptides (GH, G2H, G3H, AH, SH) to modulate the self-assembly process of giant molybdenum blue (MB) wheels yielding three different framework structures {Mo124Ce4}, {Mo122Ce5} and {Mo126Ce4} which are intimately dependent upon peptide structure and chirality. Through incorporation of oligopeptides into the cavity of MB nanowheel we can tailor the symmetry. Peptides bind on a single face of the MB wheel breaking the perpendicular 2-fold rotation axis of the parent {Mo120Ce6}. For {Mo122Ce5(G2H)3}, the odd number of peptides in the MB cavity results in incorporation of an odd number of lanthanides on the nanowheel (first time reported), leading to differences in lanthanide substitution between the coordinated face and uncoordinated layer. By using peptide ligands, we are able to tailor highly symmetrical MB nanowheels to asymmetrical hybrid superstructures.Unique chiral induction also allows us to switch the chirality of the molybdenum blue ring without altering the amino acid chirality. Subtle changes in peptide structure (GH, AH and SH) can result in a switch in the POM wheel from Δ to Λ helicity. Importantly this work suggests that the N-terminal residue has a strong homochiral directing influence while the C-terminal residue imparts a weaker heterochiral directing effect.
So up to now, we got two major results, including POM peptide automatically synthesize in peptide synthesizer and peptide modulate MB self-assembly.
