Penicillins as β-lactamase-dependent prodrugs: enabling role of a vinyl ester exocyclic to the lactam ring

2004 ◽  
pp. 2332-2333 ◽  
Author(s):  
Carol C. Ruddle ◽  
Timothy P. Smyth
Keyword(s):  
Vinyl Ester ◽  
Lactam Ring

6-Amino-2,6-dideoxy- or -2,3,6-trideoxyhexono-1,6-lactams: Synthesis and Conformation

2004 ◽  
Vol 69 (4) ◽  
pp. 867-884 ◽  
Author(s):  
Michaela Hamerníková ◽  
Jaroslav Havlíček ◽  
Romana Bláhová ◽  
Helena Pospíšilová ◽  
Hana Votavová ◽  
...  
Keyword(s):  
Low Temperature ◽  
Nmr Spectra ◽  
Ring Conformation ◽  
Water Solutions ◽  
Conformation Equilibrium ◽  
Lactam Ring ◽  
C Nmr

6-Amino-2,6-dideoxy-D-ribo-hexono-1,6-lactam (1a), 6-amino-2,6-dideoxy-D-arabino-hexono-1,6-lactam (2a), 6-amino-2,3,6-trideoxy-L-threo-hexono-1,6-lactam (3a) and per-O-acetyl derivatives 1b-3b were synthesized and their seven-membered lactam ring conformation was studied. 1H and 13C NMR spectra of the named lactams, measured at low temperature, always disclosed the presence of both 1,NC4 and 4C1,N conformations in ratios which were affected mainly by the stereochemistry of cyclohexane. There were no CD extremes over 200 nm found in water solutions of the lactams 1a and 2a, probably owing to the symmetry of the C2-C6 parts of their seven-membered rings. These results contrast with those previously found for the lactams having OH or OAc at C2, and support a concept of the directive role of the C2 substituent in conformation equilibrium.

scholarly journals Enhancement of Poly(vinyl ester) Solubility in Supercritical CO2 by Partial Fluorination: The Key Role of Polymer–Polymer Interactions

2012 ◽  
Vol 134 (29) ◽  
pp. 11920-11923 ◽  
Author(s):  
Etienne Girard ◽  
Thierry Tassaing ◽  
Séverine Camy ◽  
Jean-Stéphane Condoret ◽  
Jean-Daniel Marty ◽  
...  
Keyword(s):  
Supercritical Co2 ◽  
Vinyl Ester ◽  
Polymer Interactions

Synthetic Studies on the Role of Substituents at C-3 Position on C3-C4 Bond Cleavage of β-Lactam Ring: Convenient Route for Diastereoselective Synthesis of Pyridin-2-ones

Heterocycles ◽  
2012 ◽  
Vol 86 (2) ◽  
pp. 1301 ◽  
Author(s):  
Mohinder P. Mahajan ◽  
Pardeep Singh ◽  
Parvesh Singh ◽  
Kewal Kumar ◽  
Vipan Kumar ◽  
...  
Keyword(s):  
Bond Cleavage ◽  
Diastereoselective Synthesis ◽  
Lactam Ring ◽  
Convenient Route ◽  
Synthetic Studies

scholarly journals The Role of the Ω-Loop in Regulation of the Catalytic Activity of TEM-Type β-Lactamases

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 854 ◽  
Author(s):  
Alexey Egorov ◽  
Maya Rubtsova ◽  
Vitaly Grigorenko ◽  
Igor Uporov ◽  
Alexander Veselovsky
Keyword(s):  
Active Site ◽  
Bacterial Resistance ◽  
Structural Flexibility ◽  
Allosteric Inhibitors ◽  
Penicillin Binding Proteins ◽  
Global Challenge ◽  
Class A ◽  
Lactam Ring ◽  
Hydrolysis Of

Bacterial resistance to β-lactams, the most commonly used class of antibiotics, poses a global challenge. This resistance is caused by the production of bacterial enzymes that are termed β-lactamases (βLs). The evolution of serine-class A β-lactamases from penicillin-binding proteins (PBPs) is related to the formation of the Ω-loop at the entrance to the enzyme’s active site. In this loop, the Glu166 residue plays a key role in the two-step catalytic cycle of hydrolysis. This residue in TEM–type β-lactamases, together with Asn170, is involved in the formation of a hydrogen bonding network with a water molecule, leading to the deacylation of the acyl–enzyme complex and the hydrolysis of the β-lactam ring of the antibiotic. The activity exhibited by the Ω-loop is attributed to the positioning of its N-terminal residues near the catalytically important residues of the active site. The structure of the Ω-loop of TEM-type β-lactamases is characterized by low mutability, a stable topology, and structural flexibility. All of the revealed features of the Ω-loop, as well as the mechanisms related to its involvement in catalysis, make it a potential target for novel allosteric inhibitors of β-lactamases.

scholarly journals Interactions between active-site-serine β-lactamases and compounds bearing a methoxy side chain on the α-face of the β-lactam ring: kinetic and molecular modelling studies

1993 ◽  
Vol 293 (3) ◽  
pp. 607-611 ◽  
Author(s):  
A Matagne ◽  
J Lamotte-Brasseur ◽  
G Dive ◽  
J R Knox ◽  
J M Frère
Keyword(s):  
Water Molecule ◽  
Molecular Modelling ◽  
Side Chain ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Class A ◽  
Molecular Modelling Studies ◽  
Lactam Ring ◽  
Modelling Studies

The interactions between three class A beta-lactamases and compounds bearing a methoxy side chain on the alpha-face of the beta-lactam ring (cefoxitin, moxalactam and temocillin) have been studied. When compared with the situation prevailing with good substrates, both acylation and deacylation steps appeared to be severely impaired. Molecular modelling studies of the structures of the Henri-Michaelis complexes and of the acyl-enzymes indicate a major displacement of the crystallographically observed water molecule which connects the glutamate-166 and serine-70 side chains and underline the role of this water molecule in both reaction steps.

scholarly journals Mutational Analysis of nocK and nocL in the Nocardicin A Producer Nocardia uniformis

2005 ◽  
Vol 187 (2) ◽  
pp. 739-746 ◽  
Author(s):  
Wendy L. Kelly ◽  
Craig A. Townsend
Keyword(s):  
Natural Products ◽  
Gene Cluster ◽  
Mutational Analysis ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Wild Type ◽  
Nocardicin A ◽  
Lactam Ring ◽  
Undetermined Function

ABSTRACT The nocardicins are a family of monocyclic β-lactam antibiotics produced by the actinomycete Nocardia uniformis subsp. tsuyamanensis ATCC 21806. The most potent of this series is nocardicin A, containing a syn-configured oxime moiety, an uncommon feature in natural products. The nocardicin A biosynthetic gene cluster was recently identified and found to encode proteins in keeping with nocardicin A production, including the nocardicin N-oxygenase, NocL, in addition to genes of undetermined function, such as nocK, which bears similarities to a broad family of esterases. The latter was hypothesized to be involved in the formation of the critical β-lactam ring. While previously shown to effect oxidation of the 2′-amine of nocardicin C to provide nocardicin A, it was uncertain whether NocL was the only N-oxidizing enzyme required for nocardicin A biosynthesis. To further detail the role of NocL in nocardicin production in N. uniformis, and to examine the function of nocK, a method for the transformation of N. uniformis protoplasts to inactivate both nocK and nocL was developed and applied. A reliable protocol is reported to achieve both insertional disruption and in trans complementation in this strain. While the nocK mutant still produced nocardicin A at levels near that seen for wild-type N. uniformis, and therefore has no obvious role in nocardicin biosynthesis, the nocL disruptant failed to generate the oxime-containing metabolite. Nocardicin A production was restored in the nocL mutant upon in trans expression of the gene. Furthermore, the nocL mutant accumulated the biosynthetic intermediate nocardicin C, confirming its role as the sole oxime-forming enzyme required for production of nocardicin A.

scholarly journals A study on role of nanosized SiO2 on deformation mechanism of vinyl ester

2014 ◽  
Vol 37 (7) ◽  
pp. 1677-1683 ◽  
Author(s):  
D DEHGHAN BANIANI ◽  
S A J JAHROMI ◽  
S MOJTABA ZEBARJAD
Keyword(s):  
Deformation Mechanism ◽  
Vinyl Ester
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