scholarly journals Design of Substrate Transmembrane Mimetics as Structural Probes for γ-Secretase

2020 ◽  
Vol 142 (7) ◽  
pp. 3351-3355 ◽  
Author(s):  
Sanjay Bhattarai ◽  
Sujan Devkota ◽  
Kathleen M. Meneely ◽  
Minli Xing ◽  
Justin T. Douglas ◽  
...  
Keyword(s):  
Structural Probes

scholarly journals Monoclonal antibodies to bovine UDP-galactosyltransferase. Characterization, cross-reactivity, and utilization as structural probes.

1986 ◽  
Vol 261 (17) ◽  
pp. 7975-7981
Author(s):  
J T Ulrich ◽  
J R Schenck ◽  
H G Rittenhouse ◽  
N L Shaper ◽  
J H Shaper
Keyword(s):  
Monoclonal Antibodies ◽  
Cross Reactivity ◽  
Structural Probes

scholarly journals Fluorine-19 chemical shifts as structural probes of metal-sulfur clusters and the cofactor of nitrogenase.

1982 ◽  
Vol 79 (22) ◽  
pp. 7056-7060 ◽  
Author(s):  
P. K. Mascharak ◽  
M. C. Smith ◽  
W. H. Armstrong ◽  
B. K. Burgess ◽  
R. H. Holm
Keyword(s):  
Chemical Shifts ◽  
Structural Probes

Recent Progress in Polynuclear Ruthenium Complex-Based DNA Binders/Structural Probes and Anticancer Agents

2020 ◽  
Vol 27 (22) ◽  
pp. 3735-3752 ◽  
Author(s):  
Si-Qi Zhang ◽  
Li-Hua Gao ◽  
Hua Zhao ◽  
Ke-Zhi Wang
Keyword(s):  
Anticancer Agents ◽  
Ruthenium Complex ◽  
Ruthenium Complexes ◽  
Anticancer Activities ◽  
Bridging Ligands ◽  
Metal Centers ◽  
Dna Binders ◽  
Structural Probes ◽  
Polynuclear Ruthenium Complexes

Ruthenium complexes have stood out by several mononuclear complexes which have entered into clinical trials, such as imidazolium [trans-RuCl4(1H-imidazole)(DMSO-S)] (NAMI-A) and ([Ru(II)(4,4'-dimethyl-2,2'-bipyridine)2-(2(2'-,2'':5'',2'''-terthiophene)-imidazo[4,5-f] [1,10]phenanthroline)] 2+) (TLD-1433), opening a new avenue for developing promising ruthenium-based anticancer drugs alternative to Cisplatin. Polynuclear ruthenium complexes were reported to exhibit synergistic and/or complementary effects: the enhanced DNA structural recognition and DNA binding as well as in vitro anticancer activities. This review overviews some representative polynuclear ruthenium complexes acting as DNA structural probes, DNA binders and in vitro anticancer agents, which were developed during last decades. These complexes are reviewed according to two main categories of homo-polynuclear and hetero-polynuclear complexes, each of which is further clarified into the metal centers linked by rigid and flexible bridging ligands. The perspective, challenges and future efforts for investigations into these exciting complexes are pointed out or suggested.

scholarly journals Substitutions at Position 105 in SHV Family β-Lactamases Decrease Catalytic Efficiency and Cause Inhibitor Resistance

2012 ◽  
Vol 56 (11) ◽  
pp. 5678-5686 ◽  
Author(s):  
Mei Li ◽  
Benjamin C. Conklin ◽  
Magdalena A. Taracila ◽  
Rebecca A. Hutton ◽  
Marion J. Skalweit
Keyword(s):  
Clavulanic Acid ◽  
Susceptibility Testing ◽  
Catalytic Efficiency ◽  
Wild Type ◽  
Oxyanion Hole ◽  
Content Type ◽  
Class A ◽  
Inhibitor Resistance ◽  
Structural Probes ◽  
Variant Residue

ABSTRACTAmbler position 105 in class A β-lactamases is implicated in resistance to clavulanic acid, although no clinical isolates with mutations at this site have been reported. We hypothesized that Y105 is important in resistance to clavulanic acid because changes in positioning of the inhibitor for ring oxygen protonation could occur. In addition, resistance to bicyclic 6-methylidene penems, which are interesting structural probes that inhibit all classes of serine β-lactamases with nanomolar affinity, might emerge with substitutions at position 105, especially with nonaromatic substitutions. All 19 variants of SHV-1 with variations at position 105 were prepared. Antimicrobial susceptibility testing showed thatEscherichia coliDH10B expressing Y105 variants retained activity against ampicillin, except for the Y105L variant, which was susceptible to all β-lactams, similar to the case for the host control strain. Several variants had elevated MICs to ampicillin-clavulanate. However, all the variants remained susceptible to piperacillin in combination with a penem inhibitor (MIC, ≤2/4 mg/liter). The Y105E, -F, -M, and -R variants demonstrated reduced catalytic efficiency toward ampicillin compared to the wild-type (WT) enzyme, which was caused by increasedKm. Clavulanic acid and penemKivalues were also increased for some of the variants, especially Y105E. Mutagenesis at position 105 in SHV yields mutants resistant to clavulanate with reduced catalytic efficiency for ampicillin and nitrocefin, similar to the case for the class A carbapenemase KPC-2. Our modeling analyses suggest that resistance is due to oxyanion hole distortion. Susceptibility to a penem inhibitor is retained although affinity is decreased, especially for the Y105E variant. Residue 105 is important to consider when designing new inhibitors.

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