Carbonic Anhydrase Activators. Activation of Isoforms I, II, IV, VA, VII, and XIV withl- andd-Phenylalanine and Crystallographic Analysis of Their Adducts with Isozyme II:  Stereospecific Recognition within the Active Site of an Enzyme and Its Consequences for the Drug Design†

2006 ◽  
Vol 49 (10) ◽  
pp. 3019-3027 ◽  
Author(s):  
Claudia Temperini ◽  
Andrea Scozzafava ◽  
Daniela Vullo ◽  
Claudiu T. Supuran
Keyword(s):  
Drug Design ◽  
Carbonic Anhydrase ◽  
Active Site ◽  
Crystallographic Analysis

Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor

1997 ◽  
Vol 7 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Terry A. Lyle ◽  
Zhongguo Chen ◽  
Sandra D. Appleby ◽  
Roger M. Freidinger ◽  
Stephen J. Gardell ◽  
...  
Keyword(s):  
Active Site ◽  
Crystallographic Analysis ◽  
Thrombin Inhibitor

scholarly journals Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase

2021 ◽  
Vol 36 (1) ◽  
pp. 561-580 ◽  
Author(s):  
Alessio Nocentini ◽  
Andrea Angeli ◽  
Fabrizio Carta ◽  
Jean-Yves Winum ◽  
Raivis Zalubovskis ◽  
...  
Keyword(s):  
Drug Design ◽  
Carbonic Anhydrase ◽  
General Context ◽  
Design Studies

scholarly journals Toward the Identification of Potential α-Ketoamide Covalent Inhibitors for SARS-CoV-2 Main Protease: Fragment-Based Drug Design and MM-PBSA Calculations

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1004
Author(s):  
Mahmoud A. El Hassab ◽  
Mohamed Fares ◽  
Mohammed K. Abdel-Hamid Amin ◽  
Sara T. Al-Rashood ◽  
Amal Alharbi ◽  
...  
Keyword(s):  
Drug Design ◽  
Active Site ◽  
Binding Free Energy ◽  
Stable Complex ◽  
Active Site Residues ◽  
Structure Based Drug Design ◽  
Enzyme Active Site ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Covalent Docking

Since December 2019, the world has been facing the outbreak of the SARS-CoV-2 pandemic that has infected more than 149 million and killed 3.1 million people by 27 April 2021, according to WHO statistics. Safety measures and precautions taken by many countries seem insufficient, especially with no specific approved drugs against the virus. This has created an urgent need to fast track the development of new medication against the virus in order to alleviate the problem and meet public expectations. The SARS-CoV-2 3CL main protease (Mpro) is one of the most attractive targets in the virus life cycle, which is responsible for the processing of the viral polyprotein and is a key for the ribosomal translation of the SARS-CoV-2 genome. In this work, we targeted this enzyme through a structure-based drug design (SBDD) protocol, which aimed at the design of a new potential inhibitor for Mpro. The protocol involves three major steps: fragment-based drug design (FBDD), covalent docking and molecular dynamics (MD) simulation with the calculation of the designed molecule binding free energy at a high level of theory. The FBDD step identified five molecular fragments, which were linked via a suitable carbon linker, to construct our designed compound RMH148. The mode of binding and initial interactions between RMH148 and the enzyme active site was established in the second step of our protocol via covalent docking. The final step involved the use of MD simulations to test for the stability of the docked RMH148 into the Mpro active site and included precise calculations for potential interactions with active site residues and binding free energies. The results introduced RMH148 as a potential inhibitor for the SARS-CoV-2 Mpro enzyme, which was able to achieve various interactions with the enzyme and forms a highly stable complex at the active site even better than the co-crystalized reference.

Active-site engineering of carbonic anhydrase and its application to biosensors

2000 ◽  
pp. 221-240 ◽  
Author(s):  
Jennifer A. Hunt ◽  
Charles A. Lesburg ◽  
David W. Christianson ◽  
Richard B. Thompson ◽  
Carol A. Fierke
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site

scholarly journals Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase Inhibitory Evaluations of Benzenesulfonamide Derivatives Containing Thiazolidinone

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2418
Author(s):  
Zuo-Peng Zhang ◽  
Ze-Fa Yin ◽  
Jia-Yue Li ◽  
Zhi-Peng Wang ◽  
Qian-Jie Wu ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Docking Studies ◽  
Active Site Residues ◽  
Single Crystal Diffraction ◽  
Docking Analysis ◽  
X Ray ◽  
Active Site Cavity ◽  
Molecular Docking Analysis ◽  
Positive Controls

To find novel human carbonic anhydrase (hCA) inhibitors, we synthesized thirteen compounds by combining thiazolidinone with benzenesulfonamide. The result of the X-ray single-crystal diffraction experiment confirmed the configuration of this class of compounds. The enzyme inhibition assays against hCA II and IX showed desirable potency profiles, as effective as the positive controls. The docking studies revealed that compounds (2) and (7) efficiently bound in the active site cavity of hCA IX by forming sufficient interactions with active site residues. The fragment of thiazolidinone played an important role in the binding of the molecules to the active site.

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