Mechanism-Based Inhibition of Human Folylpolyglutamate Synthetase: Design, Synthesis, and Biochemical Characterization of a Phosphapeptide Mimic of the Tetrahedral Intermediate

Tsukamoto, Takashi; Haile, William H.; McGuire, John J.; Coward, James K.

doi:10.1006/abbi.1998.0703

Cited by 31 publications

(28 citation statements)

References 38 publications

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“…46 This approach has been used successfully with the amide-bond ligases D-Ala-D-Ala ligase 22 and FPGS. 55,56 In this review, I shall be focussing primarily on the structural details of these four amide-bond ligases, which are central to the biosynthesis of peptidoglycan. Now that the structures of the four enzymes are known, three of them in multiple conformations, analysis of the structural similarities and difference between these four ligases may aid in understanding the interrelationships that exist between their functionalities.…”

Section: The Bacterial Cell Wallmentioning

confidence: 99%

Structure, Function and Dynamics in the mur Family of Bacterial Cell Wall Ligases

Smith

2006

Journal of Molecular Biology

155

152

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Section: The Bacterial Cell Wallmentioning

confidence: 99%

Structure, Function and Dynamics in the mur Family of Bacterial Cell Wall Ligases

Smith

2006

Journal of Molecular Biology

155

152

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“…8 Methotrexate acts by inhibiting dihydrofolic acid reductase enzyme, which is required to reduce dihydrofolates into tetrahydrofolates that are necessary for the synthesis of purine nucleotides and thymidylate. 37,38 Therefore, this drug interferes with DNA synthesis, repair, and cellular replication in actively proliferating tissues such as the bone marrow. It has been demonstrated that methotrexate causes the clonal deletion of activated T cells in a mixed lymphocyte reaction.…”

Section: Sub-types Of Lgl Leukemiamentioning

confidence: 99%

T-cell and natural killer-cell large granular lymphocyte leukemia neoplasias

Watters

Liu

Loughran

2011

Leukemia & Lymphoma

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Large granular lymphocyte (LGL) leukemia is a rare disorder of cytotoxic lymphocytes. LGL cells play an integral role in the immune system and are divided into two major lineages of CD3− natural killer (NK) cells and CD3+ T cells that circulate throughout the blood in search of infected cells, in which they will make contact through a receptor ligand and induce cell death. LGLs cells are also programmed to undergo apoptosis after contact with an infected target cell; however they continue to survive in individuals with LGL leukemia. This unchecked proliferation and cytotoxicity of LGLs in patients results in autoimmunity or malignancy. Rheumatoid arthritis is the most common autoimmune condition seen in individuals with LGL leukemia; however, LGL leukemia is associated with a wide spectrum of other autoimmune diseases. Patients may also suffer from other hematological conditions including hemolytic anemia, pure red cell aplasia, and neutropenia which lead to recurrent bacterial infections. Currently, the only established treatment involves a low dose of an immunosuppressive regimen with methotrexate, in which 40–50% of patients are either resistant or do not respond. In order to establish new therapeutics it is important to understand the current state of LGL leukemia both in clinic and in basic research.

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“…[2,3] Different phosphinate analogs act as antioxidants and surface-active and flotation agents, [4,5] components of fluxes for low-temperature soldering, [6] and reductants in the protective coating of metals. [7] In addition, they find application in analytical chemistry [8] and photography.…”

Section: Introductionmentioning

confidence: 99%

Raman and surface‐enhanced Raman studies of α‐aminophosphinic inhibitors of metalloenzymes

Podstawka

Drąg

Oleksyszyn

2009

J Raman Spectroscopy

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Here, we report the nature of new di-α-amino (L 1 -L 3 ) and α-amino-α-hydroxyphosphinic (L 4 -L 6 ) acids, which are considered potential inhibitors of the aminopeptidase N, adsorbed on a colloidal silver surface by means of surface-enhanced Raman scattering (SERS) spectroscopy. In order to reveal the adsorption mechanism of these species from their SERS spectra, Fouriertransform Raman (FT-RS) spectra of these nonadsorbed molecules were measured. By examining the enhancement, shift in wavenumbers, and changes in breadth of the SERS bands due to the adsorption process, we revealed that the tilted compounds interact with the colloidal silver substrate mainly through the benzene ring, amino group, and phosphinic moiety in the following way. The benzene ring of L 2 and L 3 is 'standing up' on the colloidal silver surface, and the C-N bond is almost vertical to it, while the tilt angle between the O-P O bond and this surface is greater than 45 • . On the other hand, for L 1 , L 4 , and L 5 , the aromatic ring and C-N bond are arranged more or less tilted, and the tilt angle between the O-P O bond and the silver substrate is smaller than 45 • . The elongation of the bond to the benzene ring, the L 6 case, produces an almost horizontal orientation of the benzene ring and the O-P O bond on the silver nanoparticles.For these ligands, the complement inhibition IC 50 tested in vitro using porcine kidney leucine aminopeptidase was correlated mainly with the behavior of the O-P O and C-CH-N fragments on the silver surface.

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Mechanism-Based Inhibition of Human Folylpolyglutamate Synthetase: Design, Synthesis, and Biochemical Characterization of a Phosphapeptide Mimic of the Tetrahedral Intermediate

Cited by 31 publications

References 38 publications

Structure, Function and Dynamics in the mur Family of Bacterial Cell Wall Ligases

Structure, Function and Dynamics in the mur Family of Bacterial Cell Wall Ligases

T-cell and natural killer-cell large granular lymphocyte leukemia neoplasias

Raman and surface‐enhanced Raman studies of α‐aminophosphinic inhibitors of metalloenzymes

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