Synthesis and biological studies of c(RGDyK) conjugates of cucurbitacins

Cucurbitacins (CUCUs) are triterpenoids known to display potent cytotoxic effects; however, their clinical application is limited due to poor pharmacokinetics and systemic toxicity. This work focuses on the development of c(RGDyK)-CUCU conjugates for the selective delivery of CUCUs to integrin-overexpressing cancer cells. The activity of the conjugates against various cancer cells was studied. They exhibited a mild cytostatic effect to six cancer cell lines and a cytotoxic effect against integrin-overexpressing MCF-7 and A549 cells. Their chemical and metabolic stability was extensively studied using LC-MS analysis. The conjugates maintained high affinity for αvβ3 integrin receptors. c(RGDyK) conjugation via a PEG linker was beneficial for CUCU-D and the resulting conjugate was approximately three-times more active than the free CUCU-D in MCF7 cells. © 2021 S. Karger AG, Basel

Synthesis and Biological Evaluation of a c(RGDyK) Peptide Conjugate of SRPIN803

In the present study, SRPIN803 and c(RGDyK)-SRPIN803 hybrid compounds were efficiently synthesized and evaluated for their stability in human plasma and buffers of pH 7.4 and 5.2. The hybrids were mainly cytostatic against a panel of tested cancer cells, whereas one c(RGDyK)-SRPIN803 hybrid, geo35, was the most active compound in this screen and was cytotoxic against cell lines MCF7 and MRC5 with IC50 values of 61 and 63 μM, respectively. SRPIN803 and geo35 exhibited antiangiogenic activity in zebrafish embryos, and this effect was dose-dependent. Although c(RGDyK)-SRPIN803 hybrid compounds were found less potent compared to SRPIN803, they have shown activities interesting enough to illustrate the potential of this approach for the development of a new class of antiangiogenic compounds. © 2021 The Authors. Published by American Chemical Society

Induction of Cachexia in Mice by Systemically Administered Myostatin

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Requirements for the successful market adoption of adaptive user interfaces for accessibility

The concept of adaptive user interfaces is a promising solution for providing users with a wide range of individual needs with accessible technology. Developers only have to implement one generic solution to offer a multitude of individually optimised concrete user interfaces. Whereas a lot of technical functionalities and characteristics of adaptive user interfaces are already solved, there is still no widespread market adoption of adaptive UI technologies. This paper presents a collection of requirements for adaptive user interface systems that can enable widespread market adoption. Furthermore it identifies strategies and individual answers, how these requirements can be addressed and met in future systems building on the Prosperity4all approach. It gives a comparison of existing research solutions and how they compare with the stated requirements