Stephen M Soisson
Affiliation: Merck Research Laboratories
- Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activationStephen M Soisson
Merck Research Laboratories, POB 2000, Rahway, NJ 07065, USA
Proc Natl Acad Sci U S A 105:5337-42. 2008..The structure of the FXR:MFA-1 complex differs significantly from that of the complex with a structurally distinct agonist, fexaramine, highlighting the inherent plasticity of the receptor...
- Structural definition and substrate specificity of the S28 protease family: the crystal structure of human prolylcarboxypeptidaseStephen M Soisson
Global Structural Biology, Merck Research Laboratories, P, O, Box 4, West Point, PA 19486, USA
BMC Struct Biol 10:16. 2010..The structural basis of the different substrate specificities of the two enzymes is not understood nor has the structure of the S28 fold been described...
- Synthesis and biological evaluation of platensimycin analogsHong C Shen
Departments of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065 0900, USA
Bioorg Med Chem Lett 19:1623-7. 2009..The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity...
- Isolation, enzyme-bound structure and antibacterial activity of platencin A1 from Streptomyces platensisSheo B Singh
Merck Research Laboratories, Rahway, NJ 07065, USA
Bioorg Med Chem Lett 19:4756-9. 2009..Isolation, structure, enzyme-bound structure and activity of platencin A(1) and two other congeners have been described...
- Expression, purification and crystallization of human prolylcarboxypeptidasePravien D Abeywickrema
Global Structural Biology, Merck Research Laboratories, West Point, PA 19486, USA
Acta Crystallogr Sect F Struct Biol Cryst Commun 66:702-5. 2010..Purified PrCP yielded crystals belonging to space group R32, with unit-cell parameters a = b = 181.14, c = 240.13 A, that diffracted to better than 2.8 A resolution...
- Mechanism of action of the cell-division inhibitor PC190723: modulation of FtsZ assembly cooperativityNathaniel L Elsen
Screening and Protein Sciences, Merck Research Laboratories, West Point, Pennsylvania 19486, United States
J Am Chem Soc 134:12342-5. 2012..Together, the results reveal the molecular mechanism of FtsZ modulation by PC190723 and a conformational switch to the high-affinity state that enables polymer assembly...
- Structural basis for selective small molecule kinase inhibition of activated c-MetKeith W Rickert
Global Structural Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
J Biol Chem 286:11218-25. 2011..The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors...
- Surface-entropy reduction approaches to manipulate crystal forms of beta-ketoacyl acyl carrier protein synthase II from Streptococcus pneumoniaeGopalakrishnan Parthasarathy
Merck Research Laboratories, Rahway, NJ, USA
Acta Crystallogr D Biol Crystallogr 64:141-8. 2008..75 A resolution reveals that one of the mutations, E383A, appears to play a key role in disfavouring the less desirable triclinic crystal form and in generating a new surface for a packing interaction that stabilizes the new crystal form...
- Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagementHong C Shen
Merck Research Laboratories, Merck and Co, Inc, Rahway, NJ 07065 0900, USA
J Med Chem 52:5009-12. 2009..With minimal off-target activity and a good PK profile, the benchmark 2d exhibited remarkable in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery...
- Platensimycin is a selective FabF inhibitor with potent antibiotic propertiesJun Wang
Merck Research Laboratories, Rahway, New Jersey 07065, USA
Nature 441:358-61. 2006..Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity...
- Reducing the peptidyl features of caspase-3 inhibitors: a structural analysisJoseph W Becker
Departments of Medicinal Chemistry and Metabolic Disorders, Merck Research Laboratory, PO Box 2000, Rahway, New Jersey 07065, USA
J Med Chem 47:2466-74. 2004..These results advance the search for caspase-directed drugs by revealing how unacceptable molecular features can be removed without loss of potency...
- Restoring methicillin-resistant Staphylococcus aureus susceptibility to β-lactam antibioticsChristopher M Tan
Infectious Diseases, Merck Research Laboratories, Kenilworth, NJ 07033, USA
Sci Transl Med 4:126ra35. 2012..Collectively, these data support a target-based approach to rationally develop synergistic combination agents that mitigate drug resistance and effectively treat MRSA infections...