β-Amino acid isomers of a natural substrate of the enzyme γ-glutamyl-amino acid cyclotransferase. Synthesis of (3S)-3-aminoglutaryl-(S)-alanine and (3R)-3-aminoglutaryl-(S)-alanine

Crossley, Maxwell J.; Fisher, Megan L.; Potter, J. J.; Kuchel, Philip W.; York, Michael J.

doi:10.1039/p19900002363

Cited by 14 publications

(9 citation statements)

References 12 publications

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“…GA has been shown to have inhibitory activity (87 % at 1 m m ) when assessed using recombinant GGCT . Therefore, we evaluated the inhibitory effect of GA on GGCT activity in GGCT‐NIH‐3T3 cell homogenates.…”

Section: Resultsmentioning

confidence: 99%

“…GA has been shownt oh ave inhibitory activity (87 %a t1m m) when assessed using recombinantG GCT. [18] Therefore, we evaluated the inhibitory effect of GA on GGCT activity in GGCT-NIH-3T3c ell homogenates. GA successfully suppressed GGCT activity in the GGCT-NIH-3T3 cell homogenates nearly to the levels of the control NIH-3T3 cell homogenates (Figure 2A).…”

Section: Ga Is An Effective Ggct Inhibitor In Cell Homogenates But Nomentioning

confidence: 99%

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A Novel Prodrug of a γ‐Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer

et al. 2018

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γ-Glutamylcyclotransferase (GGCT) depletion inhibits cancer cell proliferation. However, whether the enzymatic activity of GGCT is critical for the regulation of cancer cell growth remains unclear. In this study, a novel diester-type cell-permeable prodrug, pro-GA, was developed based on the structure of N-glutaryl-l-alanine (GA), by structure optimization using temporary fluorophore-tagged prodrug candidates. The antiproliferative activity of pro-GA was demonstrated using GGCT-overexpressing NIH-3T3 cells and human cancer cells including MCF7, HL-60, and PC3 cells. By contrast, normal cells were not significantly affected by pro-GA treatment. Moreover, pro-GA administration exhibited anticancer effects in a xenograft model using immunocompromised mice inoculated with PC3 cells. These results indicate that the enzymatic activity of GGCT accelerates tumor growth and that GGCT inhibition is a promising therapeutic strategy for the treatment of GGCT-overexpressing tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Ga Is An Effective Ggct Inhibitor In Cell Homogenates But Nomentioning

confidence: 99%

A Novel Prodrug of a γ‐Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer

et al. 2018

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“…H-b 3 -AspA C H T U N G T R E N N U N G (t-Bu)-OH was prepared starting from dimethyl 3-oxoglutarate by a route previously reported by Crossley. [14] Protection of the amino group was accomplished under Schotten-Baumann conditions using Fmoc-Cl to yield the protected derivative Fmoc-b 3 -AspA C H T U N G T R E N N U N G (t-Bu)-OH 8 which was used directly in the solid phase synthesis.…”

Section: Synthesis Of Peptides 2-7mentioning

confidence: 99%

Investigating Sequence Space: How Important is the Spatial Arrangement of Functional Groups in the Asymmetric Aldol Reaction Catalyst H‐Pro‐Pro‐Asp‐NH₂?

Revell

Wennemers

2008

Adv Synth Catal

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H-Pro-Pro-Asp-NH 2 1 is a versatile catalyst for asymmetric aldol reactions. Within the catalyst structure, both the N-terminal secondary amine and the carboxylic acid are crucial for efficient catalysis. Here, the importance of the arrangement of these two functional groups towards each other was examined. Several analogues of H-Pro-Pro-Asp-NH 2 were prepared in which the secondary amine and the carboxylic acid occupy different positions. Evaluation of their catalytic properties revealed that the placement of these two functional groups is highly critical for efficient catalysis. Even seemingly small structural modifications, for example, one methylene group more or less, can modify the catalytic properties significantly. The results demonstrate the difficulty in rationally designing a peptidic catalyst and the value of combinatorial smart screening methods for catalyst discovery.Abbreviations: Fmoc = 9-fluorenylmethoxycarbonyl; HCTU = 2-(6-chloro-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; MSNT = 1-(mesitylene-2-sulfonyl)-3-nitro-1H-1,2,4-triazole; TNBS = 2,4,6-trinitrobenzenesulfonic acid.

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“…Synthesis of blastidic acid : Retrosynthetic analysis of blastidic acid ( 2 ) revealed that this β‐amino acid possesses a hidden symmetry. Therefore, the synthesis began with the preparation of chiral carboxylic acid 35 by enantioselective hydrolysis of meso ‐diester 34 32 using pig liver esterase33 (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Aminomethylation of Michael Acceptors: Complementary Radical and Polar Approaches Mediated by Dialkylzincs

Maury¹,

Mouysset²,

Feray³

et al. 2012

Chemistry A European J

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Phtalimidomethyl iodide and substituted maleimidomethyl iodide were used as radical precursors in dialkylzinc-mediated radical addition to diethyl fumarate. The reactions led stereoselectively to functionalized pyrrolizidines. The radical mechanism was supported by spin-trapping experiments and rationalized by theoretical calculations. Radical additions, on the one hand, and carbozincation followed by transmetalation with copper(I), on the other, were shown to be complementary methods to achieve the formal aminomethylation of activated unsaturated compounds.

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β-Amino acid isomers of a natural substrate of the enzyme γ-glutamyl-amino acid cyclotransferase. Synthesis of (3S)-3-aminoglutaryl-(S)-alanine and (3R)-3-aminoglutaryl-(S)-alanine

Abstract: The title compounds (VI) and (‐)‐(VIII) are potential inhibitors of the title enzyme.

Cited by 14 publications

References 12 publications

A Novel Prodrug of a γ‐Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer

A Novel Prodrug of a γ‐Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer

Investigating Sequence Space: How Important is the Spatial Arrangement of Functional Groups in the Asymmetric Aldol Reaction Catalyst H‐Pro‐Pro‐Asp‐NH₂?

Aminomethylation of Michael Acceptors: Complementary Radical and Polar Approaches Mediated by Dialkylzincs

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β-Amino acid isomers of a natural substrate of the enzyme γ-glutamyl-amino acid cyclotransferase. Synthesis of (3S)-3-aminoglutaryl-(S)-alanine and (3R)-3-aminoglutaryl-(S)-alanine

Abstract: The title compounds (VI) and (‐)‐(VIII) are potential inhibitors of the title enzyme.

Cited by 14 publications

References 12 publications

A Novel Prodrug of a γ‐Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer

A Novel Prodrug of a γ‐Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer

Investigating Sequence Space: How Important is the Spatial Arrangement of Functional Groups in the Asymmetric Aldol Reaction Catalyst H‐Pro‐Pro‐Asp‐NH2?

Aminomethylation of Michael Acceptors: Complementary Radical and Polar Approaches Mediated by Dialkylzincs

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Investigating Sequence Space: How Important is the Spatial Arrangement of Functional Groups in the Asymmetric Aldol Reaction Catalyst H‐Pro‐Pro‐Asp‐NH₂?