264887-81-2Relevant academic research and scientific papers
A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors**
Yang, Kai S.,Ma, Xinyu R.,Ma, Yuying,Alugubelli, Yugendar R.,Scott, Danielle A.,Vatansever, Erol C.,Drelich, Aleksandra K.,Sankaran, Banumathi,Geng, Zhi Z.,Blankenship, Lauren R.,Ward, Hannah E.,Sheng, Yan J.,Hsu, Jason C.,Kratch, Kaci C.,Zhao, Baoyu,Hayatshahi, Hamed S.,Liu, Jin,Li, Pingwei,Fierke, Carol A.,Tseng, Chien-Te K.,Xu, Shiqing,Liu, Wenshe Ray
supporting information, p. 942 - 948 (2020/12/15)
The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro) to digest two of its translated long polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital pr
Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety
Konno, Sho,Thanigaimalai, Pillaiyar,Yamamoto, Takehito,Nakada, Kiyohiko,Kakiuchi, Rie,Takayama, Kentaro,Yamazaki, Yuri,Yakushiji, Fumika,Akaji, Kenichi,Kiso, Yoshiaki,Kawasaki, Yuko,Chen, Shen-En,Freire, Ernesto,Hayashi, Yoshio
, p. 412 - 424 (2013/02/25)
We describe here the design, synthesis and biological evaluation of a series of molecules toward the development of novel peptidomimetic inhibitors of SARS-CoV 3CLpro. A docking study involving binding between the initial lead compound 1 and th
Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: A strategy for the design of peptidase inhibitors
Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Law, James K.,Marabout, Benoit,Luthra, Pratibha Mehta,Moore, Andrew N. J.,Peschard, Olivier,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
, p. 664 - 674 (2007/10/03)
The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase which has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO3H)-Met-OH + Gly-Trp-Met-Asp-Phe-NH2. In seeking a reversible inhibitor of this peptidase, the enzymatic binding subsites were characterized using a fluorimetric assay based on the hydrolysis of the artificial substrate Ala-Ala-Phe-amidomethylcoumarin. A series of di- and tripeptides having various alkyl or aryl side chains was studied to determine the accessible volume for binding and to probe the potential for hydrophobic interactions. From this initial study the tripeptides Ile-Pro-Ile-OH (K(i) = 1 μM) and Ala-Pro-Ala-OH (K(i) = 3 μM) and dipeptide amide Val-Nvl-NHBu (K(i) = 3 μM) emerged as leads. Comparison of these structures led to the synthesis of Val-Pro-NHBu (K(i) = 0.57 μM) which served for later optimization in the design of butabindide, a potent reversible competitive and selective inhibitor of the CCK-8-inactivating peptidase. The strategy for this work is explicitly described since it illustrates a possible general approach for peptidase inhibitor design.
