CBCHFX 15 (13) 1841–2008 (2014) · ISSN 1439-4227 · Vol. 15 · No. 13 · September 2014 D55712

13/2014

www.chembiochem.org

Minireview: Sortase-Based Bio-organic Strategies for Macromolecular Synthesis (V. Haridas)

Highlight: Replicating an Expanded Genetic Alphabet in Cells (J. C. Chaput)

A Journal of

Cover Picture

Emily R. Derbyshire*, Vanessa Zuzarte-Lu�s, Andreia D.Magalh¼es, Nobutaka Kato, Paul C. Sanschagrin, Jinhua Wang,Wenjun Zhou, Chandrasekhar V. Miduturu, Ralph Mazitschek,Piotr Sliz, Maria M. Mota, Nathanael S. Gray, and Jon Clardy*

The cover picture shows small-molecule kinase inhibitors that were identified asantimalarials by using a forward chemical genetic screen. The malaria kinase treedisplayed in the center shows parasite kinases that are predicted based on protein-sequence analyses. The background shows the lifecycle of the malaria parasite, whichincludes a mosquito vector and the infection of human liver cells, followed by invasionof red blood cells. On p. 1920 ff, E. R. Derbyshire, J. Clardy et al. explain how theycompleted this screen with a diverse array of kinase inhibitors, including severalcompounds already in clinical trials for cancer, to discover potential probes tointerrogate the malaria kinome. Several different parasite kinases were identified aspotential targets from analysis of the screening hits and the work demonstrates thatthe identified kinases are essential to both liver- and blood-parasite stages, thushighlighting the essential role of kinases to parasite biology. These findings identifiedsmall-molecule probes to explore malaria biology as well as show that the malariakinome is a target rich for disease prevention and treatment.