- Ethylene biosynthesis. 12. Analog approach to the active site topography of the ethylene-forming enzyme. Novel hydroxamate inhibitors
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In order to understand both the substrate specificity and active site topography of the ethylene-forming enzyme (EFE), a number of analogs of its substrate, 1-aminocyclopropanecarboxylic acid, have been prepared and studied as inhibitors. Because of the dependence of EFE activity on iron, hydroxamic acids, a functional group known to bind iron tightly, derived from several small carboxylic/amino acids were studied along with the parent amino acids. The activity of these materials was assayed in vitro against the purified EFE from apple fruit. The varying potency of the amino acid hydroxamates suggests that they do not act simply by binding to iron and removing it from the enzyme. The order of their potency was consistent with the idea that binding reflects both metal chelation and hydrophobic interactions in the active site. The most potent inhibitor, ACC-hydroxamate, has about 1 μM K(i).
- Pirrung,Cao,Chen
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Read Online
- Design and Synthesis of Fsp3-Rich, Bis-Spirocyclic-Based Compound Libraries for Biological Screening
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The exploration of innovative chemical space is a critical step in the early phases of drug discovery. Bis-spirocyclic frameworks occur in natural products and other biologically relevant metabolites and show attractive features, such as molecular compactness, structural complexity, and three-dimensional character. A concise approach to the synthesis of bis-spirocyclic-based compound libraries starting from readily available commercial reagents and robust chemical transformations has been developed. A number of novel bis-spirocyclic scaffold examples, as implemented in the European Lead Factory project, is presented.
- Stotani, Silvia,Lorenz, Christoph,Winkler, Matthias,Medda, Federico,Picazo, Edwige,Ortega Martinez, Raquel,Karawajczyk, Anna,Sanchez-Quesada, Jorge,Giordanetto, Fabrizio
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supporting information
p. 330 - 336
(2016/07/06)
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- ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
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Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): (Formula (I)), including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2, R3, Z1 and Z2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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Page/Page column 78
(2011/04/26)
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- PEPTIDES AND PEPTIDOMIMETIC COMPOUNDS, THE MANUFACTURING THEREOF AS WELL AS THEIR USE FOR PREPARING A THERAPEUTICALLY AND/OR PREVENTIVELY ACTIVE PHARMACEUTICAL COMPOSITION
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Peptides, peptidomimetics and derivatives thereof of the general formula I: H2N-GHRPX1-β-X4X5X6X7X8X9X10-X11 (I), in which X1-X10 denote one of the 20 genetically coded amino acids, wherein X8, X9 and X10 may also denote a single chemical bond;X11 denotes OR1 in which R1 equals hydrogen or (C1-C10) alkyl NR2R3 with R2 and R3 are equal or different and denote hydrogen, (C1-C10) alkyl, or a residue —W-PEG5-60K, in which the PEG residue is attached via a suitable spacer W to the N-atom, ora residue NH—Y-Z-PEG5-60K, in whichY denotes a chemical bond or a genetically coded amino acids from the group S, C, K or R andZ denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, and their physiologically acceptable salts, andβ denotes an amino acid, or a peptidomimetic element, which induces a bend or turn in the peptide backbone.
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- 1-CARBAMOYLCYCLOALKYLCARBOXYLIC ACID COMPOUNDS, PROCESSES FRO MAKING AND USES THEREOF
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The invention relates to the field of pharmaceutics and more specifically to novel cycloalkylamidoacid compositions useful in the preparation of cycloalkyaminoacids and oxazolidinediones, and processes for making cycloamidoacids. Formula (1)
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Page/Page column 18
(2008/06/13)
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- Hydrogen-bonded tapes based on symmetrically substituted diketopiperazines: A robust structural motif for the engineering of molecular solids
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A series of eight symmetrically substituted diketopiperazines (DKPs) derived from 1-amino-1-carboxycycloalkanes (n = 3-7; 3,3,5,5-tetramethylcyclohexane; 4,4-dimethylcyclohexane; 2-indan) were synthesized and their crystal structures determined. In the solid state, all eight compounds form two pairs of hydrogen bonds with two adjacent molecules to form a one-dimensional structure that we refer to as 'tapes'. These molecules represent a range of volumes and shapes that contain a common molecular fragment (DKP ring). We examined this series of compounds with three objectives in mind: (i) to establish the ability of the hydrogen-bonded 'tape' motif to persist through these differences in volume and shape; (ii) to provide a series of structurally related compounds to use to test computational methods of predicting crystal structure from molecular structure; (iii) to search for qualitative correlations between molecular structure and crystal packing. All compounds form tapes and with one exception, all tapes pack with their long axes parallel. When viewed down their long axis, two types of tapes emerge: planar and nonplanar. The type of tape that forms reflects the conformation adapted by the DKP ring-planar or boat. Planar tapes form when the angle (α) between the two planes defined by the cis-amides in the DKP ring is 180°; nonplanar tapes form when α 180°. Five of the eight compounds studied form planar tapes, the remaining three compounds form nonplanar tapes. Despite the variability in volume and shape represented by this series of molecules, the persistence of the tape motif in their crystalline solids suggests that the hydrogen-bonding interactions between parallel alignment of tapes that pack in a manner that permits the interdigitation of substituents on adjacent tapes.
- Palacin, Serge,Chin, Donovan N.,Simanek, Eric E.,MacDonald, John C.,Whitesides, George M.,McBride, Mary T.,Palmore, G. Tayhas R.
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p. 11807 - 11816
(2007/10/03)
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- Peptide Sweeteners. 6. Structural Studies on the C-Terminal Amino Acid of L-Aspartyl Dipeptide Sweeteners
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Stereochemical and structural aspects of the variations in the C-terminal residue of L-aspartyl-L-phenylalanine methyl ester have been investigated.Novel configurational analogues such as L-aspartyl-D-alanine benzyl ester and L-aspartyl-D-α-aminobutyric acid benzyl ester were found to be sweet.In addition, chiral and achiral α,α-dialkylglycine and α-aminocycloalkanecarboxylic acids were incorporated into the dipeptides.The L-aspartic acid based dipeptide derivatives of α-aminoisobutyric acid methyl ester, α-aminocyclopropanecarboxylic acid methyl ester, α-aminocyclobutanecarboxylic acid methyl ester, and α-aminocyclopentanecarboxylic acid methyl ester are sweet.Dipeptides with α-aminocyclohexanecarboxylic acid methyl ester and α-aminocycloheptanecarboxylic acid methyl ester are bitter, whereas the analogues with α-aminocyclooctanecarboxylic acid methyl ester, α,α-diethylglycine methyl ester, and α-aminoisobutyric acid benzyl ester are tasteless.Aspects on chirality and effective volume of the C-terminal residue are discussed and correlated with taste.
- Tsang, Joseph W.,Schmied, Bernhard,Nyfeler, Rolf,Goodman, Murray
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p. 1663 - 1668
(2007/10/02)
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