The Recognition And Control Of Polyoxometalates With Biological Molecular And Their Applications Research

Polyoxometalates(POMs) are a diverse family of metal oxide clusters, with defined architectures and variable, but controlled, sizes in the nanometer range. Among different areas of inorganic chemistry metaloxide-based POM molecular clusters represent a class of inorganic compounds that exhibit unmatched structural versatility and unique intrinsic properties.As important inorganic drug candidates, POMshave shown promising antiviral and antitumor activities for more than a decade.In recent years, POMs are found to exhibit biological activities in the aspects of antibacterial, anticancer, antiviral, and antitumor properties. For these purposes, studies on the interaction between POMs and biomolecules such as peptides or proteins have attracted much attention. So, in our recent works, we studied the interaction of HPV peptide and SA with POMs which containing different charges.Similar to HSA, bovine serum albumins(BSA) also possess typical biological functions, and play a key role in biochemical experiments such as cell culture protocols, stabilization of some enzymes and so on.Because of the well-established structural information, BSA becomes one of the most widely used model proteins.In addition, the study on the binding interaction of POMs to proteins is favorable to find out the multifunctionality of POMs at physiological conditions.Human papillomavirus(HPV) particles bind and infect to epithelial cells with high selectivity and harmful to human health.The life cycle of HPV starts with its infection to host cells by binding to specific molecules on the surface. So exploring the pathway that viruses attach on cells surface is the prerequisite to understand the viral life cycle. Early investigations have confirmed that the viral capsid proteins play a key role in the process of the viral infection, which are composed of 360 copies of major capsid proteins, L1, and a small number of minor capsid proteins, L2.In the first work, the binding induced physiochemical phenomena of a highly charged Eu-containing polyoxometalate, K13[Eu(SiW9Mo2O39)2](EuSiWMo), with a model protein, bovine serum albumin(BSA) was identified upon the examination of luminescence of both the components during the titration. The large emission enhancement and subsequently quenching of the EuSiWMo were found in close relation to the amount of added BSA. Being different from the known binding type of less charged POMs, a distinct two-step binding process was concluded and the possible mechanism was proposed through the analysis on the time-resolved fluorescence spectra, isothermal titration calorimetry(ITC), transmission electron microscope(TEM) and two-dimensional correlation spectroscopy(2D COS). The electrostatic interaction of POMs with the positive charged surface areas of protein, and the existing states of EuSi WMo were found to play important roles for the multi-step bindings. Being different from the simple Kiggen-type POMs, the present study also implied that the highly charge POMs intend to yield multi-step binding due to their intrinsic preference to aggregate, being similar as found in other systems. Therefore, it could confirm that the highly charged POMs undergo their unique process when binding with BSA. The present results also pointed out a general regularity for choosing bioactive POMs suitable for the combination with other proteins.In the second part, we conducted a ternary system,which were constituted with POMs, HPVL1/L2 peptiedes and glycosaminoglycans(GAGs). We found that the assembly containing cationic peptide and europium substituted POMs could be used as a fluorescence probe for GAGs screening through the more specific binding between peptide and GAGs. EuW10 could be used as fluorescence probe to distinguish GAGs, the important cell receptors for HPVs infection. In addition, the method could also be used to distinguish different peptidic segments, to clarify which one from capsid proteins is more important for the HPVs intrusion.It illustrated that(i) a Eu-containing POM with 9 negative charges, EuW10, is a good probe;(ii) heparin and CS are the potential cell receptors, while HA may not be;(iii) basic peptide from minor capsid protein, L2, play more important role than those from L1, for the HPVs infection on cells. The present study is meaningful in understanding the interaction between peptides, GAGs and POMs, and especially in finding novel luminescence inorganic agents for the detection of biomolecules in aqueous solution, which could be extended to other proteins and/or viruses systems by using peptides and POMs with identical properties, and finally to promote the development of anti-virus agents.