Cover Feature: Heat Shock Proteins Revisited: Using a Mutasynthetically Generated Reblastatin Library to Compare the Inhibition of Human and Leishmania Hsp90s (ChemBioChem 6/2018)

Abstract

The cover feature picture shows new reblastatin derivatives obtained by a chemo‐biosemisynthetic approach with the corresponding aminobenzoic acid derivatives as starting building blocks. The fluoro and amino derivatives exerted high inhibitory activity on human and leishmania Hsp90, whereas the presence of an alkynyl substituent leads to selective activity towards Hsp90 from leishmania. The inhibitory activity was unraveled by using a novel protein microarray system with purified Hsp90 proteins and was further confirmed by cell‐based assays and ITC measurements. More information can be found in the full paper by C. Zeilinger, A. Kirschning et al. on page 562 in Issue 6, 2018 (DOI: 10.1002/cbic.201700616).

Anticancer activity and toxicity of new quaternary ammonium geldanamycin derivative salts and their mixtures with potentiators

“…These analogues showed attractive activities against the cancer cell lines, such as human breast adenocarcinoma (SKBR-3, MCF-7, and MDA-MB-231), ovarian adenocarcinoma (SKOV-3), lung adenocarcinoma (A-549), and prostate adenocarcinoma (PC-3). 2,4,[14][15][16][17][18][19][20] Moreover, modifications at the ansa-macrolide correlated to the preparation of conjugates with biotin, foliate, or within corporated triazole bridge, that gained molecular probe features of improved biocompatibility. [21][22][23][24] Overall, the ansa-bridge modifications of GDM led to a less effective anticancer potency than those performed at the rigid benzene or benzoquinone cores.…”

Engineered Biosynthesis of Alkyne-Tagged Polyketides by Type I PKSs

“…The megasynthases themselves have been investigated and have undergone extensive engineering efforts due to their modular structures that have captured scientists' imagination with the possibility of producing on-demand, designer molecules (Awakawa et al, 2018;Barajas et al, 2017;Chemler et al, 2015;Harvey et al, 2012;Kalkreuter and Williams, 2018;Klaus and Grininger, 2018;Koryakina et al, 2017;Moss et al, 2013;Ranganathan et al, 1999;Sundermann et al, 2013;Tang et al, 2000;Wlodek et al, 2017;Yonemoto et al, 2012;. Many of these engineering strategies have included efforts geared toward the inclusion of functional chemical handles for subsequent drug discovery or chemical biology studies, albeit often employing fed precursors containing the functionality of interest (Kalkreuter et al, 2019a;Koryakina et al, 2017;Mohammadi-Ostad-Kalayeh et al, 2018).…”

Adhesiomics - Testing Protein-Protein Interaction of Cell Adhesion Proteins on Microarrays

“…Protein microarray technology was used recently for targetoriented screening of chemically synthesized compound libraries or isolated natural compounds on Heat-Shock Proteins (Hsp), since Hsps together with the accompanied stress proteome are relevant targets in cancer and pathogenic organism [1][2][3][4][5][6][7][8][9]. An extended application of this method showed recently that the microarray technology enables also studies of protein-protein interaction to enable a broader application range [4,7].…”