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  • Human neutrophil elastase HNE is a serine

    2019-07-10

    Human neutrophil elastase (HNE) is a serine protease central to the pathology in a wide range of diseases including chronic wounds, cystic fibrosis, and acute respiratory distress syndrome (Owen, 2008). Although neutrophil proteases are necessary for completion of wound healing, HNE is secreted in high titre from neutrophils in the inflammatory stage of chronic wounds, and the high concentration of HNE in chronic wounds is responsible for the breakdown of growth factors and connective tissue proteins contributing to non-healing wounds. The mechanism of action is similar to the role HNE plays in the pathophysiology of other inflammatory diseases (Yager et al., 1997). Thus, point of care protease detection of HNE has received increased attention for its clinical relevance to chronic wounds and other inflammatory diseases where expedited determination of the role of proteases in pathophysiology is critical to patient care. Previously we have assessed the relative roles of HNE substrate sensitivity by examining use of fluorogenic and chromogenic signal transduction on a wide range of cellulosic and nanocellulosic matrices (Edwards et al., 2013; Fontenot et al., 2017). In this manner, improvement in protease sensor sensitivity has been shown by enhancing substrate-enzyme recognition properties, and increasing the specific surface area of the transducer surface and the employment of colorimetric amplification and spectroscopic sensitivity with fluorescence has been assessed (Fontenot et al., 2016). More recently assessing the peptide-cellulose conjugate in terms of the relative conformational contributions of the crystalline MK 571 and the peptides conformation to the spatiotemporal influences of enzyme substrate kinetics has provided insights on design approaches to protease sensors at a molecular level (Edwards, Fontenot, Liebner, French, & Condon, 2018). To further improve the surface properties of nanocellulose, we examined the use of oxalic acid/choline treatments of cotton cellulose as an adjunct treatment to forming cotton-based nanocellulose (Ling, Edwards et al., 2018; Ling, Zhang, Yang, Takabe, & Xu, 2018). The nanocellulose derived from new kind of DES treatment may provide new strategy on controlling the properties of the nanocellulose, such as the crystal sizes, content of carboxyl groups as well as the surface area, which are critical for improving the quality of the fabricated HNE sensor. Here we describe the preparation, characterization and activity of chromogenic analogs as HNE substrate, peptide-cellulose conjugates to form a nanocellulosic transducer surface with enhanced sensor sensitivity to HNE.
    Experimental
    Results and discussion
    Conclusions
    Acknowledgements The authors gratefully acknowledged financial support by National Key Research and Development Program of China (2017YFD0601004) and Chinese Scholarship Council (CSC No. 201706510045). We also appreciate Dr Casey Grimm of USDA for mass spectral analysis.
    Introduction Many heterocyclic compounds are distinguished as active products pharmaceutically and are gaining consistent attention in the development of new drugs [1]. Heterocyclic ring contains elements other than carbon; most frequently are sulfur, nitrogen and oxygen [2]. The physicochemical properties of ring depend on the type and size of ring structure, and these properties also vary by changing the substituent attached with it [3], [4]. Heterocyclic molecules have various clinical applications and play an active role as antitumor [5], [6], antibacterial [7], anti-inflammatory [8], antiviral [9], and antifungal agents [10]. Thiazoles are very important compounds and are the significant components of large number of medicinal molecules containing important biological activities, such as antibacterial [11], anthelmintic [12], antitubercular [13], antiprotozoal [14], antifungal [15], anti-inflammatory, cardiotonic, bacterial, fungicidal, anesthetic and sedatives [16].