STRUCTURE AND REACTIONS OF CYCLOSERINE<sup>1</sup>

Hidy, Phil H.; Hodge, E. B.; Young, Vernon V.; Harned, R. L.; Brewer, Glenn A.; Phillips, W. F.; Runge, Wolfgang; Stavely, Homer E.; Pohland, Albert E; Boaz, Harold E.; Sullivan, H. R.

doi:10.1021/ja01613a106

Cited by 106 publications

(27 citation statements)

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“…Azide 10 was prepared in 84% yield from serine amide hydrochloride16 and 6-azidohexanoic acid 17. Triazole 11 was prepared in 83% yield by reaction of azide 10 with 1-hexyne at room temperature in methanol in the presence of tetrakis(acetonitrile)copper(I) hexafluorophosphate and TBTA 18.…”

Section: Resultsmentioning

confidence: 99%

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A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides

Alleti

Venkataramanarao

et al. 2010

J. Org. Chem.

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A flexible molecular scaffold bearing varying numbers of terminal alkyne groups was synthesized in five steps from solanesol. R(CO)-MSH(4)-NH 2 ligands, which have a relatively low affinity for binding at the human melanocortin 4 receptor (hMC4R), were prepared by solid phase synthesis and were N-terminally acylated using 6-azidohexanoic acid. Multiple copies of the azide N 3 (CH 2 ) 5 (CO)-MSH(4)-NH 2 were attached to the alkyne-bearing, solanesol-derived molecular scaffold via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Control studies showed that the binding affinity of the triazole-containing ligand, CH 3 (CH 2 ) 3 (C 2 N 3 )(CH 2 ) 5 (CO)-MSH(4)-NH 2 , was not significantly diminished relative to the corresponding parental ligand, CH 3 (CO)-MSH(4)-NH 2 . In a competitive binding assay using a Eu-labeled probe based on the superpotent ligand NDP-α-MSH, the monovalent and multivalent constructs appear to bind to hMC4R as monovalent species. In a similar assay using a Eu-labeled probe based on MSH(4), modest increases in binding potency with increased MSH(4) content per scaffold were observed.

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Section: Resultsmentioning

confidence: 99%

“…To a solution of serine amide hydrochloride16 (1.10 gm, 7.9 mmol) in DMF (20 mL) at room temperature was added triethylamine (0.80 g, 7.9 mmol). To the resulting white suspension was added 2,5-dioxopyrrolidin-1-yl 6-azidohexanoate17 (1.88 g, 7.1 mmol) and the reaction mixture was stirred at room temperature.…”

Section: Experimental Procedures28mentioning

confidence: 99%

A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides

Alleti

Venkataramanarao

et al. 2010

J. Org. Chem.

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“…An attempt has been made to summarize some general information with regard to the rate of heterotrophic nitrification and the maximum Lemoigne et al (1936) Steinberg (1939 Saris and Virtanen (1957) Shirata et al (1970) Wiley et al (1965) Dulaney (1963; Kaczka et al (1962) Neilands (1967) MacDonald (1961) MacDonald (1962 l=' Neilands (1967) l=' Micetich Sing et al (1966) ~ Neilands (1967) <: Hidy et al (1955) III f!l.…”

Section: Growth and Distributionmentioning

confidence: 99%

Biochemical Ecology of Nitrification and Denitrification

Verstraete

Focht

1977

Advances in Microbial Ecology

628

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“…-Cycloserine (DCS), a cyclic structural analogue of D-alanine, is produced by Streptomyces garyphalus and S. lavendulae (1). DCS prevents the actions of both alanine racemase (2, 3) and D-alanyl-D-alanine ligase (4,5), which are necessary for the biosynthesis of the bacterial cell wall.…”

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Crystallographic Study To Determine the Substrate Specificity of an l -Serine-Acetylating Enzyme Found in the d -Cycloserine Biosynthetic Pathway

et al. 2013

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DcsE, one of the enzymes found in the D-cycloserine biosynthetic pathway, displays a high sequence homology to L-homoserine O-acetyltransferase (HAT), but it prefers L-serine over L-homoserine as the substrate. To clarify the substrate specificity, in the present study we determined the crystal structure of DcsE at a 1.81-Å resolution, showing that the overall structure of DcsE is similar to that of HAT, whereas a turn region to form an oxyanion hole is obviously different between DcsE and HAT: in detail, the first and last residues in the turn of DcsE are Gly 52 and Pro 55 , respectively, but those of HAT are Ala and Gly, respectively. In addition, more water molecules were laid on one side of the turn region of DcsE than on that of HAT, and a robust hydrogenbonding network was formed only in DcsE. We created a HAT-like mutant of DcsE in which Gly 52 and Pro 55 were replaced by Ala and Gly, respectively, showing that the mutant acetylates L-homoserine but scarcely acetylates L-serine. The crystal structure of the mutant DcsE shows that the active site, including the turn and its surrounding waters, is similar to that of HAT. These findings suggest that a methyl group of the first residue in the turn of HAT plays a role in excluding the binding of L-serine to the substrate-binding pocket. In contrast, the side chain of the last residue in the turn of DcsE may need to form an extensive hydrogen-bonding network on the turn, which interferes with the binding of L-homoserine.

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STRUCTURE AND REACTIONS OF CYCLOSERINE¹

Cited by 106 publications

References 0 publications

A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides

A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides

Biochemical Ecology of Nitrification and Denitrification

Crystallographic Study To Determine the Substrate Specificity of an l -Serine-Acetylating Enzyme Found in the d -Cycloserine Biosynthetic Pathway

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STRUCTURE AND REACTIONS OF CYCLOSERINE1

Cited by 106 publications

References 0 publications

A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides

A Solanesol-Derived Scaffold for Multimerization of Bioactive Peptides

Biochemical Ecology of Nitrification and Denitrification

Crystallographic Study To Determine the Substrate Specificity of an l -Serine-Acetylating Enzyme Found in the d -Cycloserine Biosynthetic Pathway

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STRUCTURE AND REACTIONS OF CYCLOSERINE¹