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PUBLICATIONS: NEW


Discovery of novel mutant selective EGFR kinase inhibitors effective against EGFR T790M.
Zhou W, Ercan D, Chen L, Yun C-H, Li D, Capelletti M, Chirieac L, Iacob RE, Padera R, Engen JR, Wong K-K,
Eck MJ, Gray NS & Janne PA.
Nature 2009. In press.

ABSTRACT
To be released upon publication.

Pubmed: too new


Gas-phase hydrogen/deuterium exchange in a travelling wave ion guide for the examination of protein conformations.
Rand KD, Pringle SD, Murphy JP 3rd, Fadgen KE, Brown J, Engen JR.
Anal. Chem. 2009. In press. DOI: 10.1021/ac901897x

ABSTRACT
Accumulating evidence suggests that solution-phase conformations of small globular proteins and large molecular protein assemblies can be preserved for milliseconds after electrospray ionization.  Thus, the study of proteins in the gas-phase on this time-scale is highly desirable. Here we demonstrate that a travelling wave ion guide (TWIG) of a Synapt mass spectrometer offers a highly suitable environment for rapid and efficient gas-phase hydrogen/deuterium exchange (HDX).  Gaseous ND3 was introduced into either the source TWIG or the TWIG located just after the ion mobility cell, such that ions underwent HDX as they passed through the ND3 on the way to the time-of-flight analyzer.  The extent of deuterium labeling could be controlled by varying the quantity of ND3 or the speed of the travelling wave.  The gas-phase HDX of model peptides corresponded to labeling of primarily fast exchanging sites due to the short labeling times (ranging from 0.1 to 10 ms).  In addition to peptides, gas-phase HDX of ubiquitin, cytochrome c, lysozyme and apomyoglobin were examined.  We conclude that HDX of protein ions in a TWIG is highly sensitive to protein conformation, enables the detection of conformers present on sub-milliseconds timescales and can readily be combined with ion mobility spectrometry.  
 
Pubmed: 19921790


Targeting wild-type and T315I Bcr-Abl by combining allosteric with ATP-site inhibitors.
Zhang J, Adrián FJ, Jahnke W, Cowan-Jacob SW, Li AG, Iacob RE, Sim T, Powers J, Dierks C, Sun F, Guo GR, Ding Q, Okram B, Choi Y, Wojciechowski A, Deng X, Liu G, Fendrich G, Strauss A, Vajpai N, Grzesiek S, Tuntland T, Liu Y, Bursulaya B, Azam M, Manley PW, Engen JR, Daley GQ, Warmuth M & Gray NS.
Nature 2009. In press.

ABSTRACT
To be released upon publication.

Pubmed: too new


Analysis of Protein Conformation and Dynamics by Hydrogen / Deuterium Exchange MS.

  Engen JR.
Anal. Chem. 2009. Oct 1;81(19):7870-5.

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ABSTRACT
Understanding as much as possible about proteins in the shortest amount of time has long been a goal of hydrogen exchange (HX) MS.  Recent advances have led to improvements in the technique, but has this goal yet been achieved?

Pubmed: 19788312