© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Editor-in-Chief: Natalia Ortúzar
Impact Factor: 2.968
ISI Journal Citation Reports © Ranking: 2014: 19/59 (Chemistry Medicinal); 83/255 (Pharmacology & Pharmacy)
Online ISSN: 1860-7187
November 24, 2015
Editor's Picks: Issue 12/2015
The Editor's picks for issue 12 report studies that address aberrant lipid metabolism. The Full Paper by Overkleeft, Aerts, and colleagues is focused on three enzymes involved in the metabolism of glucosylceramide, while another Full Paper by Tacke and co-workers discusses silicon-containing agonists of receptors that mediate antilipolytic effects. Read more...
Recently Published Articles
- The Lysosomal Protein Saposin B Binds Chloroquine
Dr. Brian P. Huta, Matthew R. Mehlenbacher, Yan Nie, Xuelei Lai, Dr. Chloe Zubieta, Prof. Fadi Bou-Abdallah and Prof. Robert P. Doyle
Article first published online: 30 NOV 2015 | DOI: 10.1002/cmdc.201500494
Unravelling the mystery of CQ: The full extent of chloroquine (CQ) pharmacology in humans remains unclear. Herein, using isothermal titration calorimetry (ITC) and fluorescence quenching experiments, we demonstrate that the lysosomal protein saposin B (sapB), critical for select lipid degradation, binds CQ with implications for CQ function and toxicity. Additionally, the X-ray crystal structure of sapB–CQ, the first complete crystal structure of sapB with a small-molecule substrate, shows one molecule of CQ bind to the sapB dimer.
- Identification of Small-Molecule Inhibitors of the Antiapoptotic Protein Myeloid Cell Leukaemia-1 (Mcl-1)
Dr. Andrew M. Beekman, Dr. Maria A. O'Connell and Dr. Lesley A. Howell
Article first published online: 30 NOV 2015 | DOI: 10.1002/cmdc.201500488
Breaking up the party: Overexpression of the antiapoptosis Bcl-2 protein family members is commonly observed in cancers, with myeloid cell leukemia-1 (Mcl-1) often being responsible for resistance to radio and chemotherapy. Exploiting the Mcl-1 selective apoptosis regulating protein Noxa, novel small molecules capable of modulating Mcl-1 are identified and evaluated.
- Serpin A1 C-Terminal Peptides as Collagen Turnover Modulators
Simona Pascarella, Dr. Caterina Tiberi, Dr. Giuseppina Sabatino, Dr. Francesca Nuti, Prof. Anna Maria Papini, Prof. Lisa Giovannelli and Prof. Paolo Rovero
Article first published online: 30 NOV 2015 | DOI: 10.1002/cmdc.201500472
Time to heal: A) Synthesis of overlapping peptides of serpin A1 C-terminal portion: SA1-I, SA1-II, SA1-III. B) Biological screening on cultured normal human dermal fibroblasts: dose–response curve for peptide SA1-III. Our data highlight that this decapeptide is a promising lead compound for further development in the search for wound-healing agents to be included in future pharmaceutical formulas.
- Design, Synthesis and Evaluation of Triazole-Pyrimidine Analogues as SecA Inhibitors
Jianmei Cui, Jinshan Jin, Arpana Sagwal Chaudhary, Ying-hsin Hsieh, Hao Zhang, Chaofeng Dai, Krishna Damera, Weixuan Chen, Phang C. Tai and Binghe Wang
Article first published online: 26 NOV 2015 | DOI: 10.1002/cmdc.201500447
One stone, several birds! The SecA inhibitors discovered in this study are broad-spectrum antimicrobials with the intrinsic ability to null the effect of efflux pumps. They are therefore effective against multidrug-resistant bacterial strains, can inhibit virulence factor secretion, and are very active against strains of bacteria that are resistant to antibiotics in current use, including vancomycin.
- Inspired by Nature: The 3-Halo-4,5-dihydroisoxazole Moiety as a Novel Molecular Warhead for the Design of Covalent Inhibitors
Dr. Andrea Pinto, Dr. Lucia Tamborini, Dr. Gregorio Cullia, Prof. Paola Conti and Prof. Carlo De Micheli
Article first published online: 26 NOV 2015 | DOI: 10.1002/cmdc.201500496
A hint from Nature: 3-Halo-4,5-dihydroisoxazole, a component of the naturally occurring antibiotic acivicin, is a powerful warhead for the covalent inhibition of target enzymes. Here, we describe the use of this moiety in medicinal chemistry to develop covalent inhibitors of parasitic and bacterial enzymes, and human targets involved in the modulation of neuronal metabolic pathways or tumor cell metabolism.