Highlighted Text:
Show |
Hide
Full text loading...
Chapter 8 : Inhibition of Class A β-Lactamases
Authors:
Samy O. Meroueh1,
Jooyoung Cha2,
Shahriar Mobashery3
VIEW AFFILIATIONS
HIDE AFFILIATIONS
Affiliations:
1: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556;
2: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556;
3: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556
Content Type: Monograph
Publication Year:
2007
Category: Bacterial Pathogenesis
Book DOI:
10.1128/9781555815615
Chapter DOI:
10.1128/9781555815615.ch8
MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Preview this chapter:
Inhibition of Class A β-Lactamases, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815615/9781555813031_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555815615/9781555813031_Chap08-2.gif
Abstract:
The catalytic function of β-lactamases is the primary mechanism of bacterial resistance to β-lactam antibiotics (penicillins, cephalosporins, carbapenems). β-lactamases hydrolyze the β-lactam bond of these antibiotics, a structure modification that abrogates the antibacterial activity. β-lactams include tazobactam, a highly effective sulfone penam inhibitor, penicillanic acid sulfone sulbactam, 6-β-bromopenicillanic acid, and thienamycin. Clavulanate is a potent inhibitor of class A β-lactamases, which incidentally exhibits weak antimicrobial activity as well. A series of molecules-using sulfoxide and sulfone penams have been synthesized as starting points-with sulfhydryl and sulfide moieties at C-6; the goal of this exercise was to arrive at molecules that would simultaneously inhibit classes A and B of β-lactamases. The study also confirmed that the sulfone oxidation state of the penam thiazolidine resulted in greater inhibition. The success of BRL 42715 prompted additional efforts into compounds with a double bond at C-6, leading to the discovery of SYN-1012-with a methyl triazolyl moiety at C6 instead-and another more recent methylidene penem-with a bicyclic and heterocyclic moiety at C-6; both of these compounds show good activity against class A and C β-lactamases. Several routes have been taken towards the development of more effective inhibitors including the syntheses of variants of penam sulfones, penems, alkylidenes, monobactams, transition-state analogs, and the boronates.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
Key Concept Ranking
- beta-Lactam Antibiotics
- 0.5467328
- Ionization Mass Spectrometry
- 0.42942533
0.5467328
Figures
Inhibition of Class A β-Lactamases
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815615.ch08-1,webId=/content/author/10.1128/9781555815615.ch08-1,properties={foaf_givenname=Samy O., foaf_name=Samy O. Meroueh, foaf_surname=Meroueh, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815615.ch08-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815615.ch08-2,webId=/content/author/10.1128/9781555815615.ch08-2,properties={foaf_givenname=Jooyoung, foaf_name=Jooyoung Cha, foaf_surname=Cha, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815615.ch08-aff2]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555815615.ch08-3,webId=/content/author/10.1128/9781555815615.ch08-3,properties={foaf_givenname=Shahriar, foaf_name=Shahriar Mobashery, foaf_surname=Mobashery, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555815615.ch08-aff3]]}]]
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig01
Figure 8.1
Stereoview of the three-dimensional structure of TEM-1 β-lactamase shown in ribbon representation (Protein Data Bank [PDB] code 1BTL). (B) Stereoview of a close-up of the active site of TEM-1 showing Glu-166 (9 o’clock), Lys-73 (11 o’clock), Ser-130 (12 o’clock), Lys-234 (2 o’clock), and Ser-70 (center). The enzyme is shown in ribbon representation, and residues are shown in capped-sticks representation. The conserved water molecule is shown as a sphere. (C) Stereoview of the acyl enzyme complex of a deacylation-deficient TEM β-lactamase in complex with benzylpenicillin (PDB code 1TEM). The enzyme is rendered in ribbon representation, and residues Glu-166 (9 o’clock), Lys-73 (12 o’clock), Ser-130 (1 o’clock), and Lys-234 (3 o’clock) are shown in capped sticks. An arrow is used to point to the C-6 side chain of the bound benzylpenicillin. The hydrolytic water is shown as a sphere.
10.1128/9781555815615/f0102-01_thmb.gif
10.1128/9781555815615/f0102-01.gif
Figure 8.1
Stereoview of the three-dimensional structure of TEM-1 β-lactamase shown in ribbon representation (Protein Data Bank [PDB] code 1BTL). (B) Stereoview of a close-up of the active site of TEM-1 showing Glu-166 (9 o’clock), Lys-73 (11 o’clock), Ser-130 (12 o’clock), Lys-234 (2 o’clock), and Ser-70 (center). The enzyme is shown in ribbon representation, and residues are shown in capped-sticks representation. The conserved water molecule is shown as a sphere. (C) Stereoview of the acyl enzyme complex of a deacylation-deficient TEM β-lactamase in complex with benzylpenicillin (PDB code 1TEM). The enzyme is rendered in ribbon representation, and residues Glu-166 (9 o’clock), Lys-73 (12 o’clock), Ser-130 (1 o’clock), and Lys-234 (3 o’clock) are shown in capped sticks. An arrow is used to point to the C-6 side chain of the bound benzylpenicillin. The hydrolytic water is shown as a sphere.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig02
Figure 8.2
Chemical structures of some inhibitors of class A β-lactamases.
10.1128/9781555815615/f0103-01_thmb.gif
10.1128/9781555815615/f0103-01.gif
Figure 8.2
Chemical structures of some inhibitors of class A β-lactamases.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig03
Figure 8.3
Chemistry of inhibition of class A β-lactamases by clavulanate.
10.1128/9781555815615/f0104-01_thmb.gif
10.1128/9781555815615/f0104-01.gif
Figure 8.3
Chemistry of inhibition of class A β-lactamases by clavulanate.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig04
Figure 8.4
Chemistry of inhibition of class A β-lactamases by tazobactam.
10.1128/9781555815615/f0105-01_thmb.gif
10.1128/9781555815615/f0105-01.gif
Figure 8.4
Chemistry of inhibition of class A β-lactamases by tazobactam.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig05
Figure 8.5
(A) Stereoview of the active site of SHV-1 showing intermediates 16 and 22 (Protein Data Bank [PDB] code 1G56). The bottom arrows point to 16, while the top arrow points to 22. The protein is rendered in ribbon, while Ser-70 (covalently bound to inhibitor; center), Glu-166 (10 o’clock), Lys-73 (12 o’clock), Ser-130 (covalently bound to inhibitor; 1 o’clock), and Lys-234 (3 o’clock) are shown in capped-sticks representation. (B) Intermediate 18 shown in the active site of SHV-2. The arrows point to the bound inhibitor that is attached to Ser-70 (center). Lys-73 (12 o’clock), Ser-130 (1 o’clock), and Lys-234 (2 o’clock) are shown in capped-sticks representation (PDB code 1RCJ).
10.1128/9781555815615/f0105-02_thmb.gif
10.1128/9781555815615/f0105-02.gif
Figure 8.5
(A) Stereoview of the active site of SHV-1 showing intermediates 16 and 22 (Protein Data Bank [PDB] code 1G56). The bottom arrows point to 16, while the top arrow points to 22. The protein is rendered in ribbon, while Ser-70 (covalently bound to inhibitor; center), Glu-166 (10 o’clock), Lys-73 (12 o’clock), Ser-130 (covalently bound to inhibitor; 1 o’clock), and Lys-234 (3 o’clock) are shown in capped-sticks representation. (B) Intermediate 18 shown in the active site of SHV-2. The arrows point to the bound inhibitor that is attached to Ser-70 (center). Lys-73 (12 o’clock), Ser-130 (1 o’clock), and Lys-234 (2 o’clock) are shown in capped-sticks representation (PDB code 1RCJ).
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig06
Figure 8.6
Chemical structures of penam sulfone (
23
) and derivatives.
10.1128/9781555815615/f0106-01_thmb.gif
10.1128/9781555815615/f0106-01.gif
Figure 8.6
Chemical structures of penam sulfone ( 23 ) and derivatives.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig07
Figure 8.7
Synthetic inhibitors based on the structure of 6-(nitrileoxidomethyl)penam sulfone active in inhibition of classes A, B, and C of β-lactamases.
10.1128/9781555815615/f0106-02_thmb.gif
10.1128/9781555815615/f0106-02.gif
Figure 8.7
Synthetic inhibitors based on the structure of 6-(nitrileoxidomethyl)penam sulfone active in inhibition of classes A, B, and C of β-lactamases.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig08
Figure 8.8
Chemical structures of additional inhibitors based on the penam sulfone nucleus.
10.1128/9781555815615/f0106-03_thmb.gif
10.1128/9781555815615/f0106-03.gif
Figure 8.8
Chemical structures of additional inhibitors based on the penam sulfone nucleus.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig09
Figure 8.9
Chemical structures of representative carbapenems.
10.1128/9781555815615/f0107-01_thmb.gif
10.1128/9781555815615/f0107-01.gif
Figure 8.9
Chemical structures of representative carbapenems.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig10
Figure 8.10
Inhibitory mechanism of β-lactamase by carbapenems.
10.1128/9781555815615/f0107-02_thmb.gif
10.1128/9781555815615/f0107-02.gif
Figure 8.10
Inhibitory mechanism of β-lactamase by carbapenems.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig11
Figure 8.11
Synthetic carbapenem derivatives that serve as inhibitors of classes A and C of β-lactamases.
10.1128/9781555815615/f0108-01_thmb.gif
10.1128/9781555815615/f0108-01.gif
Figure 8.11
Synthetic carbapenem derivatives that serve as inhibitors of classes A and C of β-lactamases.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig12
Figure 8.12
Inhibitory mechanism of penem BRL 42715 (
47
).
10.1128/9781555815615/f0109-01_thmb.gif
10.1128/9781555815615/f0109-01.gif
Figure 8.12
Inhibitory mechanism of penem BRL 42715 ( 47 ).
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig13
Figure 8.13
Stereoview of intermediate (
49
) bound to the active site of SHV-1 (Protein Data Bank [PDB] code 1ONH). The enzyme is shown in ribbon representation, while the bound ligand and active-site residues Glu-166 (9 o’clock), Lys-73 (11 o’clock), Ser-130 (12 o’clock), Lys-234 (2 o’clock), and Arg-244 (5 o’clock) are shown in capped-sticks representation. The arrows point to the thiazepine intermediate that is bound to Ser-70.
10.1128/9781555815615/f0109-02_thmb.gif
10.1128/9781555815615/f0109-02.gif
Figure 8.13
Stereoview of intermediate ( 49 ) bound to the active site of SHV-1 (Protein Data Bank [PDB] code 1ONH). The enzyme is shown in ribbon representation, while the bound ligand and active-site residues Glu-166 (9 o’clock), Lys-73 (11 o’clock), Ser-130 (12 o’clock), Lys-234 (2 o’clock), and Arg-244 (5 o’clock) are shown in capped-sticks representation. The arrows point to the thiazepine intermediate that is bound to Ser-70.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig14
Figure 8.14
Inhibitory mechanism of monobactam derivative 53 against class A β-lactamases.
10.1128/9781555815615/f0110-01_thmb.gif
10.1128/9781555815615/f0110-01.gif
Figure 8.14
Inhibitory mechanism of monobactam derivative 53 against class A β-lactamases.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig15
Figure 8.15
Schematic of phosphonate interactions with nucleophiles.
10.1128/9781555815615/f0110-02_thmb.gif
10.1128/9781555815615/f0110-02.gif
Figure 8.15
Schematic of phosphonate interactions with nucleophiles.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig16
Figure 8.16
Chemical structure of synthetic phosphonate-based transition-state analog inhibitors.
10.1128/9781555815615/f0110-03_thmb.gif
10.1128/9781555815615/f0110-03.gif
Figure 8.16
Chemical structure of synthetic phosphonate-based transition-state analog inhibitors.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig17
Figure 8.17
Chemical structure of cyclic phosphonate-based transition-state analog inhibitors.
10.1128/9781555815615/f0111-01_thmb.gif
10.1128/9781555815615/f0111-01.gif
Figure 8.17
Chemical structure of cyclic phosphonate-based transition-state analog inhibitors.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig18
Figure 8.18
Chemical structure of boronate transition-state analog inhibitors.
10.1128/9781555815615/f0111-02_thmb.gif
10.1128/9781555815615/f0111-02.gif
Figure 8.18
Chemical structure of boronate transition-state analog inhibitors.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig19
Figure 8.19
Chemical structure of a potent boronate inhibitor.
10.1128/9781555815615/f0111-03_thmb.gif
10.1128/9781555815615/f0111-03.gif
Figure 8.19
Chemical structure of a potent boronate inhibitor.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
/content/10.1128/9781555815615.ch08.ch08fig20
Figure 8.20
Cephalosporin-based inhibitors and the inhibitory mechanism against class C β-lactamases.
10.1128/9781555815615/f0111-04_thmb.gif
10.1128/9781555815615/f0111-04.gif
Figure 8.20
Cephalosporin-based inhibitors and the inhibitory mechanism against class C β-lactamases.
Citation:
Meroueh S, Cha J, Mobashery S.
2007.
Inhibition of Class A β-Lactamases,
p 101-114.
In
Bonomo R, Tolmasky M (ed),
Enzyme-Mediated Resistance to Antibiotics.
ASM Press, Washington, DC.
doi: 10.1128/9781555815615.ch8
References
/content/book/10.1128/9781555815615.ch08
1.
Bitha, P.,, Z. Li,, G. D. Francisco,, Y. Yang,, P. J. Petersen,, E. Lenoy, and, Y. I. Lin. 1999. 6-(1-Hydroxyalkyl)penam sulfone derivatives as inhibitors of class A and class C beta-lactamases II. Bioorg. Med. Chem. Lett. 9: 997– 1002.
2.
Bonfiglio, G.,, G. Russo, and, G. Nicoletti. 2002. Recent developments in carbapenems. Expert Opin. Investig. Drugs 11: 529– 544.
3.
Bradley, J. S.,, J. Garau,, H. Lode,, K. V. Rolston,, S. E. Wilson, and, J. P. Quinn. 1999. Carbapenems in clinical practice: a guide to their use in serious infection. Int. J. Antimicrob. Agents 11: 93– 100.
4.
Brown, A. G.,, D. Butterworth,, M. Cole,, G. Hanscomb,, J. D. Hood,, C. Reading, and, G. N. Rolinson. 1976. Naturally-occurring beta-lactamase inhibitors with antibacterial activity. J. Antibiot. (Tokyo) 29: 668– 669.
5.
Brown, R. P.,, R. T. Aplin, and, C. J. Schofield. 1996. Inhibition of TEM-2 beta-lactamase from Escherichia coli by clavulanic acid: observation of intermediates by electrospray ionization mass spectrometry. Biochemistry 35: 12421– 12432.
6.
Bulychev, A.,, J. R. Bellettini,, M. O’Brien,, P. J. Crocker,, J. P. Samama,, M. J. Miller, and, S. Mobashery. 2000. N-sulfonyloxy-beta-lactam inhibitors for beta-lactamases. Tetrahedron 56: 5719– 5728.
7.
Bulychev, A.,, I. Massova,, S. A. Lerner, and, S. Mobashery. 1995. Penem Brl-42715—an effective inactivator for beta-lactamases. J. Am. Chem. Soc. 117: 4797– 4801.
8.
Buynak, J. D.,, H. Chen,, L. Vogeti,, V. R. Gadhachanda,, C. A. Buchanan,, T. Palzkill,, R. W. Shaw,, J. Spencer, and, T. R. Walsh. 2004. Penicillin-derived inhibitors that simultaneously target both metallo- and serine-beta-lactamases. Bioorg. Med. Chem. Lett. 14: 1299– 1304.
9.
Buynak, J. D.,, A. S. Rao,, V. R. Doppalapudi,, G. Adam,, P. J. Petersen, and, S. D. Nidamarthy. 1999. The synthesis and evaluation of 6-alkylidene-2’beta-substituted penam sulfones as beta-lactamase inhibitors. Bioorg. Med. Chem. Lett. 9: 1997– 2002.
10.
Buynak, J. D.,, K. Wu,, B. Bachmann,, D. Khasnis,, L. Hua,, H. K. Nguyen, and, C. L. Carver. 1995. Synthesis and biological activity of 7-alkylidenecephems. J. Med. Chem. 38: 1022– 1034.
11.
Charnas, R. L.,, J. Fisher, and, J. R. Knowles. 1978. Chemical studies on inactivation of Escherichia coli RTEM beta-lactamase by clavulanic acid. Biochemistry 17: 2185– 2189.
12.
Chen, C. C. H., and, O. Herzberg. 1992. Inhibition of beta-lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies. J. Mol. Biol. 224: 1103– 1113.
13.
Crichlow, G. V.,, M. Nukaga,, V. R. Doppalapudi,, J. D. Buynak, and, J. R. Knox. 2001. Inhibition of class C beta-lactamases: structure of a reaction intermediate with a cephem sulfone. Biochemistry 40: 6233– 6239.
14.
Crompton, I. E.,, B. K. Cuthbert,, G. Lowe, and, S. G. Waley. 1988. Beta-lactamase inhibitors. The inhibition of serine beta-lactamases by specific boronic acids. Biochem. J. 251: 453– 459.
15.
English, A. R.,, J. A. Retsema,, A. E. Girard,, J. E. Lynch, and, W. E. Barth. 1978. CP-45,899, a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactams: initial bacteriological characterization. Antimicrob. Agents Chemother. 14: 414– 419.
16.
Farmer, T. H.,, J. W. J. Page,, D. J. Payne, and, D. J. C. Knowles. 1994. Kinetic and physical studies of beta-lactamase inhibition by a novel penem, Brl-42715. Biochem. J. 303: 825– 830.
17.
Fisher, J. 1984. β-Lactams resistant to hydrolysis by the β-lactamases, p. 33– 79. In L. E. Bryan (ed.), Antimicrobial Drug Resistance. Academic Press, Orlando, Fla.
18.
Helfand, M. S.,, M. A. Totir,, M. P. Carey,, A. M. Hujer,, R. A. Bonomo, and, P. R. Carey. 2003. Following the reactions of mechanism-based inhibitors with beta-lactamase by Raman crystallography. Biochemistry 42: 13386– 13392.
19.
Imtiaz, U.,, E. Billings,, J. R. Knox,, E. K. Manavathu,, S. A. Lerner, and, S. Mobashery. 1993. Inactivation of class-A beta-lactamases by clavulanic acid—the role of arginine-244 in a proposed nonconcerted sequence of events. J. Am. Chem. Soc. 115: 4435– 4442.
20.
Jelsch, C.,, F. Lenfant,, J. M. Masson, and, J. P. Samama. 1992. Beta-lactamase TEM1 of E. coli. Crystal structure determination at 2.5 A resolution. FEBS Lett. 299: 135– 142.
21.
Kahan, J. S.,, F. M. Kahan,, R. Goegelman,, S. A. Currie,, M. Jackson,, E. O. Stapley,, T. W. Miller,, A. K. Miller,, D. Hendlin,, S. Mochales,, S. Hernandez,, H. B. Woodruff, and, J. Birnbaum. 1979. Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties. J. Antibiot. (Tokyo) 32: 1– 12.
22.
Knowles, J. R. 1985. Penicillin resistance. The chemistry of beta-lactamase inhibition. Acc. Chem. Res. 18: 97– 104.
23.
Knox, J. R.,, P. C. Moews,, W. A. Escobar, and, A. L. Fink. 1993. A catalytically-impaired class-a beta-lactamase: 2 A crystal structure and kinetics of the Bacillus licheniformis E166a mutant. Protein Eng. 6: 11– 18.
24.
Kuzin, A. P.,, M. Nukaga,, Y. Nukaga,, A. Hujer,, R. A. Bonomo, and, J. R. Knox. 2001. Inhibition of the SHV-1 beta-lactamase by sulfones: crystallographic observation of two reaction intermediates with tazobactam. Biochemistry 40: 1861– 1866.
25.
Li, N. X., and, R. F. Pratt. 1998. Inhibition of serine beta-lactamases by acyl phosph(on)ates: new source of inert acyl [and phosphyl] enzymes. J. Am. Chem. Soc. 120: 4264– 4268.
26.
Livermore, D. M., and, H. Y. Chen. 1997. Potentiation of beta-lactams against Pseudomonas aeruginosa strains by Ro 48-1256, a bridged monobactam inhibitor of AmpC beta-lactamases. J. Antimicrob. Chemother. 40: 335– 343.
27.
Matagne, A.,, P. Ledent,, D. Monnaie,, A. Felici,, M. Jamin,, X. Raquet,, M. Galleni,, D. Klein,, I. Francois, and, J. M. Frere. 1995. Kinetic study of interaction between BRL 42715, beta-lactamases, and D-alanyl-D-alanine peptidases. Antimicrob. Agents Chemother. 39: 227– 231.
28.
Maveyraud, L.,, I. Massova,, C. Birck,, K. Miyashita,, J. P. Samama, and, S. Mobashery. 1996. Crystal structure of 6 alpha-(hydroxymethyl)penicillanate complexed to the TEM-1 beta-lactamase from Escherichia coli: evidence on the mechanism of action of a novel inhibitor designed by a computer-aided process. J. Am. Chem. Soc. 118: 7435– 7440.
29.
Maveyraud, L.,, L. Mourey,, L. P. Kotra,, J. D. Pedelacq,, V. Guillet,, S. Mobashery, and, J. P. Samama. 1998. Structural basis for clinical longevity of carbapenem antibiotics in the face of challenge by the common class A beta-lactamases from the antibiotic-resistant bacteria. J. Am. Chem. Soc. 120: 9748– 9752.
30.
Miyashita, K.,, I. Massova,, P. Taibi, and, S. Mobashery. 1995. Design, synthesis, and evaluation of a potent mechanism-based inhibitor for the TEM beta-lactamase with implications for the enzyme mechanism. J. Am. Chem. Soc. 117: 11055– 11059.
31.
Moews, P. C.,, J. R. Knox,, O. Dideberg,, P. Charlier, and, J. M. Frere. 1990. Beta-lactamase of Bacillus licheniformis 749/ C at 2 A resolution. Proteins 7: 156– 171.
32.
Mourey, L.,, K. Miyashita,, P. Swaren,, A. Bulychev,, J. P. Samama, and, S. Mobashery. 1998. Inhibition of the NMC-A beta-lactamase by a penicillanic acid derivative and the structural bases for the increase in substrate profile of this antibiotic resistance enzyme. J. Am. Chem. Soc. 120: 9382– 9383.
33.
Ness, S.,, R. Martin,, A. M. Kindler,, M. Paetzel,, M. Gold,, S. E. Jensen,, J. B. Jones, and, N. C. J. Strynadka. 2000. Structure-based design guides the improved efficacy of deacylation transition state analogue inhibitors of TEM-1 beta-lactamase. Biochemistry 39: 5312– 5321.
34.
Nishida, K.,, C. Kunugita,, T. Uji,, F. Higashitani,, A. Hyodo,, N. Unemi,, S. N. Maiti,, O. A. Phillips,, P. Spevak,, K. P. Atchison,, S. M. Salama,, H. Atwal, and, R. G. Micetich. 1999. In vitro and in vivo activities of Syn2190, a novel beta-lactamase inhibitor. Antimicrob. Agents Chemother. 43: 1895– 1900.
35.
Nukaga, M.,, T. Abe,, A. M. Venkatesan,, T. S. Mansour,, R. A. Bonomo, and, J. R. Knox. 2003. Inhibition of class A and class C beta-lactamases by penems: crystallographic structures of novel 1,4-thiazepine intermediate. Biochemistry 42: 13152– 13159.
36.
Padayatti, P. S.,, M. S. Helfand,, M. A. Totir,, M. P. Carey,, A. M. Hujer,, P. R. Carey,, R. A. Bonomo, and, F. van den Akker. 2004. Tazobactam forms a stoichiometric trans-enamine intermediate in the E166A variant of SHV-1 beta-lactamase: 1.63 angstrom crystal structure. Biochemistry 43: 843– 848.
37.
Page, M. G. 2000. β-Lactamase inhibitors. Drug. Resist. Updat. 3: 109– 125.
38.
Page, M. I., and, A. P. Laws. 1998. The mechanism of catalysis and the inhibition of beta-lactamases. Chem. Commun. 1998: 1609– 1617.
39.
Phillips, O. A.,, D. P. Czajkowski,, P. Spevak,, M. P. Singh,, C. Hanehara-Kunugita,, A. Hyodo,, R. G. Micetich, and, S. N. Maiti. 1997. SYN-1012: a new beta-lactamase inhibitor of penem skeleton. J. Antibiot. (Tokyo) 50: 350– 356.
40.
Pratt, R. F. 1989. Inhibition of a class C beta-lactamase by a specific phosphonate monoester. Science 246: 917– 919.
41.
Pratt, R. F., and, N. J. Hammar. 1998. Salicyloyl cyclic phosphate, a “penicillin-like” inhibitor of beta-lactamases. J. Am. Chem. Soc. 120: 3004– 3006.
42.
Rahil, J., and, R. F. Pratt. 1992. Mechanism of inhibition of the class C beta-lactamase of Enterobacter cloacae P99 by phosphonate monoesters. Biochemistry 31: 5869– 5878.
43.
Rice, L. B., and, R. A. Bonomo. 2000. β-Lactamases: which ones are clinically important? Drug Resist. Updat. 3: 178– 189.
44.
Sandanayaka, V. P.,, G. B. Feigelson,, A. S. Prashad,, Y. J. Yang, and, P. J. Petersen. 2001. Allyl and propargyl substituted penam sulfones as versatile intermediates toward the syntheses of new beta-lactamase inhibitors. Bioorg. Med. Chem. Lett. 11: 997– 1000.
45.
Sandanayaka, V. P., and, A. S. Prashad. 2002. Resistance to beta-lactam antibiotics: structure and mechanism based design of beta-lactamase inhibitors. Curr. Med. Chem. 9: 1145– 1165.
46.
Sandanayaka, V. P., and, Y. J. Yang. 2000. Dipolar cycloaddition of novel 6-(nitrileoxidomethyl) penam sulfone: an efficient route to a new class of beta-lactamase inhibitors. Org. Lett. 2: 3087– 3090.
47.
Shah, P. M., and, R. D. Isaacs. 2003. Ertapenem, the first of a new group of carbapenems. J. Antimicrob. Chemother. 52: 538– 542.
48.
Strynadka, N. C.,, H. Adachi,, S. E. Jensen,, K. Johns,, A. Sielecki,, C. Betzel,, K. Sutoh, and, M. N. James. 1992. Molecular structure of the acyl-enzyme intermediate in beta-lactam hydrolysis at 1.7 A resolution. Nature 359: 700– 705.
49.
Tabei, K.,, X. Feng,, A. M. Venkatesan,, T. Abe,, U. Hideki,, T. S. Mansour, and, M. M. Siegel. 2004. Mechanism of inactivation of beta-lactamases by novel 6-methylidene penems elucidated using electrospray ionization mass spectrometry. J. Med. Chem. 47: 3674– 3688.
50.
Taibi, P., and, S. Mobashery. 1995. Mechanism of turnover of imipenem by the TEM beta-lactamase revisited. J. Am. Chem. Soc. 117: 7600– 7605.
51.
Therrien, C., and, R. C. Levesque. 2000. Molecular basis of antibiotic resistance and beta-lactamase inhibition by mechanism-based inactivators: perspectives and future directions. FEMS Microbiol. Rev. 24: 251– 262.
52.
Wang, X. J.,, G. Minasov, and, B. K. Shoichet. 2002. Nonco-valent interaction energies in covalent complexes: TEM-1 beta-lactamase and beta-lactams. Protein. Struct. Funct. Genet. 47: 86– 96.
53.
Wise, R.,, J. M. Andrews, and, N. Patel. 1981. 6-Beta-bromo-and 6-beta-iodo penicillanic acid, two novel beta-lactamase inhibitors. J. Antimicrob. Chemother. 7: 531– 536.
54.
Yang, Y.,, K. Janota,, K. Tabei,, N. Huang,, M. M. Siegel,, Y. I. Lin,, B. A. Rasmussen, and, D. M. Shlaes. 2000. Mechanism of inhibition of the class A beta-lactamases PC1 and TEM-1 by tazobactam. Observation of reaction products by electro-spray ionization mass spectrometry. J. Biol. Chem. 275: 26674– 26682.