scholarly journals In Silico Identification and Experimental Validation of Distal Activity-Enhancing Mutations in Tryptophan Synthase

ACS Catalysis ◽  
2021 ◽  
pp. 13733-13743
Author(s):  
Miguel A. Maria-Solano ◽  
Thomas Kinateder ◽  
Javier Iglesias-Fernández ◽  
Reinhard Sterner ◽  
Sílvia Osuna
Keyword(s):  
In Silico ◽  
Experimental Validation ◽  
Tryptophan Synthase ◽  
In Silico Identification

scholarly journals In silico identification and experimental validation of hits active against KPC-2 β-lactamase

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0203241 ◽  
Author(s):  
Raphael Klein ◽  
Pasquale Linciano ◽  
Giuseppe Celenza ◽  
Pierangelo Bellio ◽  
Sofia Papaioannou ◽  
...  
Keyword(s):  
In Silico ◽  
Experimental Validation ◽  
In Silico Identification

scholarly journals In silico identification and experimental validation of amino acid motifs required for the Rho-of-plants GTPase-mediated activation of receptor-like cytoplasmic kinases

2018 ◽  
Vol 37 (4) ◽  
pp. 627-639 ◽  
Author(s):  
Dézi Bianka Lajkó ◽  
Ildikó Valkai ◽  
Mónika Domoki ◽  
Dalma Ménesi ◽  
Györgyi Ferenc ◽  
...  
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Experimental Validation ◽  
In Silico Identification

scholarly journals In Silico Identification and Experimental Validation of Novel KPC-2 β-lactamase Inhibitors

2018 ◽  
Author(s):  
R. Klein ◽  
P. Linciano ◽  
G. Celenza ◽  
P. Bellio ◽  
S. Papaioannou ◽  
...  
Keyword(s):  
In Silico ◽  
Experimental Validation ◽  
Bacterial Resistance ◽  
Treatment Options ◽  
Structural Requirement ◽  
Covalent Inhibitors ◽  
Lactam Antibiotic ◽  
Resistant Strains ◽  
In Silico Identification

AbstractBacterial resistance has become a worldwide concern, particularly after the emergence of resistant strains overproducing carbapenemases. Among these, the KPC-2 carbapenemase represents a significant clinical challenge, being characterized by a broad substrate spectrum that includes aminothiazoleoxime and cephalosporins such as cefotaxime. Moreover, strains harboring KPC-type β-lactamases are often reported as resistant to available β-lactamase inhibitors (clavulanic acid, tazobactam and sulbactam). Therefore, the identification of novel non β-lactam KPC-2 inhibitors is strongly necessary to maintain treatment options. This study explored novel, non-covalent inhibitors active against KPC-2, as putative hit candidates. We performed a structure-based in silico screening of commercially available compounds for non-β-lactam KPC-2 inhibitors. Thirty-two commercially available high-scoring, fragment-like hits were selected for in vitro validation and their activity and mechanism of action vs the target was experimentally evaluated using recombinant KPC-2. N-(3-(1H-tetrazol-5-yl)phenyl)-3-fluorobenzamide (11a), in light of its ligand efficiency (LE = 0.28 kcal/mol/non-hydrogen atom) and chemistry, was selected as hit to be directed to chemical optimization to improve potency vs the enzyme and explore structural requirement for inhibition in KPC-2 binding site. Further, the compounds were evaluated against clinical strains overexpressing KPC-2 and the most promising compound reduced the MIC of the β-lactam antibiotic meropenem by four fold.

scholarly journals In silico identification and experimental validation of cellular uptake by a new cell penetrating peptide P1 derived from MARCKS

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1637-1648
Author(s):  
Linlin Chen ◽  
Xiangli Guo ◽  
Lidan Wang ◽  
Jingping Geng ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
In Silico ◽  
Experimental Validation ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating ◽  
In Silico Identification
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