LXIX.—Benzyl δ-chlorobutyl ether: a new unsymmetrical derivative of tetramethylene glycol

Bennett, G. M.; Hock, Alfred Louis

doi:10.1039/jr9270000472

Cited by 13 publications

(3 citation statements)

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“…(A) Benzyl-(2-iodoethyl)ether (5a) (45,(54)(55)(56)(57)(58)(59) General Procedure for Ketones 6a-e. To a solution of ethylacetoacetate sodium salt (22.0 g, 144.6 mmol) in anhydrous DME (200 mL) at room temperature was added a solution of the iodide 5a-e (72.3 mmol) in anhydrous DME (50 mL), and the reaction mixture was heated at reflux overnight. After cooling to room temperature, a solution of NaOH (16.0 g, 400.0 mmol) in water (160 mL) was added, and the mixture was refluxed for 2 h, cooled to room temperature, acidified with 50% H 2 SO 4 (40 mL, final pH ∼2), and then refluxed for 2 h more.…”

Section: Methodsmentioning

confidence: 99%

Protein Farnesyltransferase Isoprenoid Substrate Discrimination Is Dependent on Isoprene Double Bonds and Branched Methyl Groups

Micali

et al. 2001

Biochemistry

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Farnesylation is a posttranslational lipid modification in which a 15-carbon farnesyl isoprenoid is linked via a thioether bond to specific cysteine residues of proteins in a reaction catalyzed by protein farnesyltransferase (FTase). We synthesized the benzyloxyisoprenyl pyrophosphate (BnPP) series of transferable farnesyl pyrophosphate (FPP) analogues (1a-e) to test the length dependence of the isoprenoid substrate on the FTase-catalyzed transfer of lipid to protein substrate. Kinetic analyses show that pyrophosphates 1a-e and geranyl pyrophosphate (GPP) transfer with a lower efficiency than FPP whereas geranylgeranyl pyrophosphate (GGPP) does not transfer at all. While a correlation was found between K(m) and analogue hydrophobicity and length, there was no correlation between k(cat) and these properties. Potential binding geometries of FPP, GPP, GGPP, and analogues 1a-e were examined by modeling the molecules into the active site of the FTase crystal structure. We found that analogue 1d displaces approximately the same volume of the active site as does FPP, whereas GPP and analogues 1a-c occupy lesser volumes and 1e occupies a slightly larger volume. Modeling also indicated that GGPP adopts a different conformation than the farnesyl chain of FPP, partially occluding the space occupied by the Ca(1)a(2)X peptide in the ternary X-ray crystal structure. Within the confines of the FTase pocket, the double bonds and branched methyl groups of the geranylgeranyl chain significantly restrict the number of possible conformations relative to the more flexible lipid chain of analogues 1a-e. The modeling results also provide a molecular explanation for the observation that an aromatic ring is a good isostere for the terminal isoprene of FPP.

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Section: Methodsmentioning

confidence: 99%

Protein Farnesyltransferase Isoprenoid Substrate Discrimination Is Dependent on Isoprene Double Bonds and Branched Methyl Groups

Micali

et al. 2001

Biochemistry

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“…and treated with HC1 to yield 4-(benzyloxy)butylamine hydrochloride (35-40% overall yield). In the second method, 4-(benzyloxy)butyronitrile prepared from 3-(benzyloxy)propyl bromide and NaCN in dimethyl sulfoxide (Bennett & Hock, 1927;Friedman & Shechter, 1960) was reduced with boranedimethyl sulfide (Brown et al, 1982) to yield 4-(benzyloxy)butylamine hydrochloride (80% overall yield). The Fmoc group was removed with piperidine.…”

Section: Methodsmentioning

confidence: 99%

Helix-Forming Tendencies of Amino Acids in Short (Hydroxybutyl)-L-glutamine Peptides: An Evaluation of the Contradictory Results from Host-Guest Studies and Short Alanine-Based Peptides

Padmanabhan

York²,

Gera³

et al. 1994

Biochemistry

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The helix propensities ("s-values") of amino acids measured using short alanine-based peptides are different, in both magnitude and rank order, from those found using random sequence copolymers of a "guest" amino acid and a (hydroxyalkyl)-L-glutamine "host". The origin of these differences is investigated here. In short alanine-based peptides containing 1-5 (hydroxybutyl)-, (hydroxypropyl)-, or (hydroxyethyl)-L-glutamines (HBQ, HPQ, and HEQ, respectively), we find the rank order of helix propensities to be Ala > HBQ > HPQ > HEQ, which is consistent with earlier results for HBQ, HPQ, and HEQ homopolymers and is attributed to helix-stabilizing hydrophobic interactions [Lotan, N., Yaron, A., & Berger, A. (1966) Biopolymers 4, 365-368]. The apparent s-values of nonpolar amino acids in a 17-residue, HBQ-based peptide cluster around 1, as they do in the host-guest studies, but in contrast to results with alanine-based peptides. The differences between the host-guest results and results obtained using alanine-based peptides may be rationalized in terms of side-chain interactions involving the hydroxyalkyl moiety.

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“…Caled for Ci8H2406: C, 64.27; , 71.9. Found: C, 64.40; H, 7.27. Ethyl c-Benzyloxy-/S-ketocaproate (5).-Ethyl Y-benzyloxy-9ketobutyrylmalonate (84 g, 0.25 mole) was boiled with 1000 ml of 2 N acetic acid for 6 hr. Carbon dioxide evolved during this time.…”

mentioning

confidence: 99%

Synthesis of carolic acid

Sudo¹,

Kaneda²,

Itoh³

1967

J. Org. Chem.

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LXIX.—Benzyl δ-chlorobutyl ether: a new unsymmetrical derivative of tetramethylene glycol

Cited by 13 publications

References 0 publications

Protein Farnesyltransferase Isoprenoid Substrate Discrimination Is Dependent on Isoprene Double Bonds and Branched Methyl Groups

Protein Farnesyltransferase Isoprenoid Substrate Discrimination Is Dependent on Isoprene Double Bonds and Branched Methyl Groups

Helix-Forming Tendencies of Amino Acids in Short (Hydroxybutyl)-L-glutamine Peptides: An Evaluation of the Contradictory Results from Host-Guest Studies and Short Alanine-Based Peptides

Synthesis of carolic acid

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