Browsing CHEM Faculty Scholarship by Author "Alliston, Kevin R."
Now showing items 21-36 of 36
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Mode of substrate interaction and energetics of carbon-oxygen bond formation of the dopamine beta-monooxygenase reaction
Wimalasena, Kandatege; Alliston, Kevin R. (American Chemical Society, 1999-11-09)Previous studies have shown that the dopamine beta-monooxygenase (DbetaM; E.C. 1.14.17.1)/1-(2-aminoethyl)-1,4-cyclohexadiene (CHDEA) reaction partitions between side chain and ring H-abstraction to produce the ... -
Neutrophil elastase inhibitors
Groutas, William C.; Dou, Dengfeng; Alliston, Kevin R. (Informa Healthcare, 2011-03-01)INTRODUCTION: Chronic obstructive pulmonary disease (COPD) constitutes a worldwide health problem. There is currently an urgent and unmet need for the development of small molecule therapeutics capable of blocking and/or ... -
Noncovalent inhibitors of human leukocyte elastase based on the 4-imidazolidinone scaffold
Wei, Liuqing; Gan, Xiangdong; Zhong, Jiaying; Alliston, Kevin R.; Groutas, William C. (Elsevier, 2003-11-17)A central problem associated with the design of enzyme inhibitors in general, and serine protease inhibitors in particular, is the identification of templates capable of binding to the active site of an enzyme in a predictable ... -
Oxadiazole-based cell permeable macrocyclic transition state inhibitors of norovirus 3CL protease
Damalanka, Vishnu C.; Kim, Yunjeong; Alliston, Kevin R.; Weerawarna, Pathum M.; Kankanamalage, Anushka C. Galasiti; Lushington, Gerald H.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Chang, Kyeong-Ok; Groutas, William C. (American Chemical Society, 2016-03-10)Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or ... -
Potent inhibition of human leukocyte elastase by 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamide derivatives
Lai, Zhong; Gan, Xiangdong; Wei, Liuqing; Alliston, Kevin R.; Yu, Hongyi; Li, Yue He; Groutas, William C. (Elsevier, 2004-09-15)The design, synthesis, and in vitro biochemical evaluation of a class of mechanism-based inhibitors of human leukocyte elastase (HLE) that incorporate in their structure a 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold ... -
Potent inhibition of norovirus 3CL protease by peptidyl α-ketoamides and α-ketoheterocycles
Mandadapu, Sivakoteswara Rao; Weerawarna, Pathum M.; Gunnam, Mallikarjuna Reddy; Alliston, Kevin R.; Lushington, Gerald H.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2012-05-26)A series of structurally-diverse α-ketoamides and α-ketoheterocycles was synthesized and subsequently investigated for inhibitory activity against norovirus 3CL protease in vitro, as well as anti-norovirus activity in a ... -
Potent inhibition of norovirus by dipeptidyl α-hydroxyphosphonate transition state mimics
Mandadapu, Sivakoteswara Rao; Gunnam, Mallikarjuna Reddy; Kankanamalage, Anushka C. Galasiti; Uy, Roxanne Adeline Z.; Alliston, Kevin R.; Lushington, Gerald H.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2013-11)The design, synthesis, and evaluation of a series of dipeptidyl α-hydroxyphosphonates is reported. The synthesized compounds displayed high anti-norovirus activity in a cell-based replicon system, as well as high enzyme ... -
Potent inhibition of Norwalk virus by cyclic sulfamide derivatives
Dou, Dengfeng; Tiew, Kok-Chuan; He, Guijia; Mandadapu, Sivakoteswara Rao; Aravapalli, Sridhar; Alliston, Kevin R.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2011-10-15)A new class of compounds that exhibit anti-norovirus activity in a cell-based system and embody in their structure a cyclosulfamide scaffold has been identified. The structure of the initial hit (compound 2a, ED(50) 4 µM, ... -
Potent norovirus inhibitors based on the acyclic sulfamide scaffold
Dou, Dengfeng; Tiew, Kok-Chuan; Mandadapu, Sivakoteswara Rao; Gunnam, Mallikarjuna Reddy; Alliston, Kevin R.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2012-03-15)The development of small molecule therapeutics to combat norovirus infection is of considerable interest from a public health perspective because of the highly contagious nature of noroviruses. A series of amino acid-derived ... -
Potential protease inhibitors based on a functionalized cyclic sulfamide scaffold
Zhong, Jiaying; Gan, Xiangdong; Alliston, Kevin R.; Lai, Zhong; Yu, Hongyi; Groutas, Christopher S.; Wong, Tzutshin; Groutas, William C. (American Chemical Society, 2004-07-01)Exploratory studies related to the design and synthesis of functionalized cyclic sulfamides (I) as potential inhibitors of proteolytic enzymes were carried out. The structural motif and three diversity sites embodied in ... -
Serendipitous discovery of an unexpected rearrangement leads to two new classes of potential protease inhibitors
Zhong, Jiaying; Lai, Zhong; Groutas, Christopher S.; Wong, Tzutshin; Gan, Xiangdong; Alliston, Kevin R.; Eichhorn, David M.; Hoidal, John R.; Groutas, William C. (Elsevier, 2004-12-01)The pathogenesis of a range of human diseases arises from the aberrant activity of proteolytic enzymes. Agents capable of selectively modulating the activity of these enzymes are of potential therapeutic value. Thus, there ... -
Structure-based design and optimization of dipeptidyl inhibitors of norovirus 3CL protease
Kankanamalage, Anushka C. Galasiti; Weerawarna, Pathum M.; Uy, Roxanne Adeline Z.; Mandadapu, Sivakoteswara Rao; Alliston, Kevin R.; Chang, Kyeong-Ok; Kim, Yunjeong; Lovell, Scott; Hua, Duy H.; Prior, Allan M.; Groutas, William C. (American Chemical Society, 2014-08-10)Human noroviruses are the primary cause of sporadic and epidemic acute gastroenteritis in the US and worldwide. Noroviruses constitute an important public health problem, as well as a potential bioterrorism threat. The ... -
Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease: Structural, biochemical, spectroscopic, and antiviral studies
Weerawarna, Pathum M.; Kim, Yunjeong; Kankanamalage, Anushka C. Galasiti; Damalanka, Vishnu C.; Lushington, Gerald H.;; Alliston, Kevin R.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Chang, Kyeong-Ok; Groutas, William C. (Elsevier B.V., 2016-08-25)Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus infections. A potentially ... -
Structure-guided design and optimization of dipeptidyl inhibitors of Norovirus 3CL protease. Structure-activity relationships and biochemical, x-ray crystallographic, cell-based, and in vivo studies
Kankanamalage, Anushka C. Galasiti; Kim, Yunjeong; Weerawarna, Pathum M.; Uy, Roxanne Adeline Z.; Damalanka, Vishnu C.; Mandadapu, Sivakoteswara Rao; Alliston, Kevin R.; Mehzabeen, Nurjahan; Battaile, Kevin P.; Lovell, Scott; Chang, Kyeong-Ok; Groutas, William C. (American Chemical Society, 2015-04-09)Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus ... -
Utilization of the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide scaffold in the design of potential inhibitors of human neutrophil proteinase 3
Dou, Dengfeng; He, Guijia; Li, Yi; Lai, Zhong; Wei, Liuqing; Alliston, Kevin R.; Lushington, Gerald H.; Eichhorn, David M.; Groutas, William C. (Elsevier, 2010-02-01)The S' subsites of human neutrophil proteinase 3 (Pr 3) were probed by constructing diverse libraries of compounds based on the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide using combinational and click chemistry methods. The ... -
X-ray snapshot of the mechanism of inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives
Huang, Weijun; Yamamoto, Yasufumi; Li, Yi; Dou, Dengfeng; Alliston, Kevin R.; Hanzlik, Robert P.; Williams, Todd D.; Groutas, William C. (American Chemical Society, 2008-04-10)The mechanism of action of a general class of mechanism-based inhibitors of serine proteases, including human neutrophil elastase (HNE), has been elucidated by determining the X-ray crystal structure of an enzyme-inhibitor ...