CHARACTERIZATION OF INTERACTION BETWEEN WHEY PROTEIN ISOLATE AND XANTHAN/CURDLAN HYDROGEL TO IMPROVE FREEZE-THAW STABILITY

Syneresis, the liquid separation from a food product, is one of the major challenges in the frozen food industry. It is often accelerated by unintentional temperature fluctuations, i.e. repeated freezing and thawing during distribution, transportation, storage, and consumption. It has been demonstrated that the combination of xanthan and curdlan is capable of reducing syneresis up to five freeze-thaw cycles (FTCs) with relatively stable rheological and textural properties. The present study aimed at developing an effective mixture of whey protein isolate (WPI) and xanthan-curdlan hydrogel complex (XCHC) to minimize moisture migration over multiple FTCs. The addition of XCHC to WPI solution significantly reduced the syneresis of heat-induced gels, increased the storage modulus (G') of the gels, reduced the minimum concentration of whey protein isolate required to form a gel, and minimized the discrepancies of G' in frequency sweep tests over 5 FTCs. By comparing the microstructure of mixed WPI-XCHC and pure WPI gels, it was found that XCHC served as a pore-forming agent, namely increasing the porosity, reducing the pore size, and consequently improving the gel's water retention over multiple FTCs. Results from dynamic rheological measurements showed that both G' and the gelation temperature of mixed WPI-XCHC complex were strongly pH-dependent. Moreover, the interactions between WPI and XCHC in aqueous solution were characterized. An edible coating solution containing the mixture of WPI, xanthan, and curdlan was tested on mushroom and green bell pepper. Fresh mushroom and green bell pepper samples treated with WPI-XCHC significantly prevented moisture migration after 10 days of frozen storage. The coating also decreased the changes of whiteness and greenness in mushroom and bell pepper, respectively, while significantly improved the firmness of bell peppers. Such information could provide useful guidelines when designing novel food products utilizing the unique properties provided by WPI-XCHC

Discovery of short-course antiwolbachial quinazolines for elimination of filarial worm infections

Parasitic filarial nematodes cause debilitating infections in people in resource-limited countries. A clinically validated approach to eliminating worms uses a 4- to 6-week course of doxycycline that targets Wolbachia, a bacterial endosymbiont required for worm viability and reproduction. However, the prolonged length of therapy and contraindication in children and pregnant women have slowed adoption of this treatment. Here, we describe discovery and optimization of quinazolines CBR417 and CBR490 that, with a single dose, achieve >99% elimination of Wolbachia in the in vivo Litomosoides sigmodontis filarial infection model. The efficacious quinazoline series was identified by pairing a primary cell-based high-content imaging screen with an orthogonal ex vivo validation assay to rapidly quantify Wolbachia elimination in Brugia pahangi filarial ovaries. We screened 300,368 small molecules in the primary assay and identified 288 potent and selective hits. Of 134 primary hits tested, only 23.9% were active in the worm-based validation assay, 8 of which contained a quinazoline heterocycle core. Medicinal chemistry optimization generated quinazolines with excellent pharmacokinetic profiles in mice. Potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease and in vitro selectivity against Loa loa (a safety concern in endemic areas). The favorable efficacy and in vitro safety profiles of CBR490 and CBR417 further support these as clinical candidates for treatment of filarial infections