Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and Evaluation of Novel Iminosugars Prepared from Natural Amino Acids.

ABSTRACT: Cyclopropanated iminosugars have a locked conformation that may enhance the inhibitory activity and selectivity against different glycosidases. We show the synthesis of new cyclopropane-containing piperidines bearing five stereogenic centers from natural amino acids l-serine and l-alanine. Those prepared from the latter amino acid may mimic l-fucose, a natural-occurring monosaccharide involved in many molecular recognition events. Final compounds prepared from l-serine bear S configurations on the C5 position. The synthesis involved a stereoselective cyclopropanation reaction of an ?,?-unsaturated piperidone, which was prepared through a ring-closing metathesis. The final compounds were tested as possible inhibitors of different glycosidases. The results, although, in general, with low inhibition activity, showed selectivity, depending on the compound and enzyme, and in some cases, an unexpected activity enhancement was observed.

SUBMITTER: Puet A

PROVIDER: S-EPMC7828477 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and Evaluation of Novel Iminosugars Prepared from Natural Amino Acids.

Puet Alejandro A Domínguez Gema G Cañada Francisco Javier FJ Pérez-Castells Javier J

Molecules (Basel, Switzerland) 20210113 2

Cyclopropanated iminosugars have a locked conformation that may enhance the inhibitory activity and selectivity against different glycosidases. We show the synthesis of new cyclopropane-containing piperidines bearing five stereogenic centers from natural amino acids l-serine and l-alanine. Those prepared from the latter amino acid may mimic l-fucose, a natural-occurring monosaccharide involved in many molecular recognition events. Final compounds prepared from l-serine bear <i>S</i> configuratio ...[more]

PMID: 33451060

Similar Datasets

Rewiring protein synthesis: From natural to synthetic amino acids.

Project description:BACKGROUND:The protein synthesis machinery uses 22 natural amino acids as building blocks that faithfully decode the genetic information. Such fidelity is controlled at multiple steps and can be compromised in nature and in the laboratory to rewire protein synthesis with natural and synthetic amino acids. SCOPE OF REVIEW:This review summarizes the major quality control mechanisms during protein synthesis, including aminoacyl-tRNA synthetases, elongation factors, and the ribosome. We will discuss evolution and engineering of such components that allow incorporation of natural and synthetic amino acids at positions that deviate from the standard genetic code. MAJOR CONCLUSIONS:The protein synthesis machinery is highly selective, yet not fixed, for the correct amino acids that match the mRNA codons. Ambiguous translation of a codon with multiple amino acids or complete reassignment of a codon with a synthetic amino acid diversifies the proteome. GENERAL SIGNIFICANCE:Expanding the genetic code with synthetic amino acids through rewiring protein synthesis has broad applications in synthetic biology and chemical biology. Biochemical, structural, and genetic studies of the translational quality control mechanisms are not only crucial to understand the physiological role of translational fidelity and evolution of the genetic code, but also enable us to better design biological parts to expand the proteomes of synthetic organisms. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.

| S-EPMC5511583 | biostudies-literature

Synthesis and evaluation of photoreactive tetrazole amino acids.

Project description:Six photoreactive tetrazole amino acids were efficiently synthesized either by the de novo Kakehi tetrazole synthesis method or by alkylation of a glycine Schiff base with tetrazole-containing alkyl halides, and four of them showed excellent reactivity toward a simple alkene in the photoinduced 1,3-dipolar cycloaddition reaction in acetonitrile/PBS buffer (1:1) mixture.

| S-EPMC2737276 | biostudies-literature

Amino Acid-Based Synthesis and Glycosidase Inhibition of Cyclopropane-Containing Iminosugars.

Project description:Synthesis of four iminosugars fused to a cyclopropane ring is described using l-serine as the chiral pool. The key steps are large-scale preparation of an α,β-unsaturated piperidinone followed by completely stereoselective sulfur ylide cyclopropanation. Stereochemistry of compounds has been studied by nuclear Overhauser effect spectroscopy (NOESY) experiments and 1H homonuclear decoupling to measure constant couplings. The activity of these compounds against different glycosidases has been evaluated. Although inhibition activity was low (compound 8a presents a (K i) of 1.18 mM against β-galactosidase from Escherichia coli), interestingly, we found that compounds 8a and 8b increase the activity of neuraminidase from Vibrio cholerae up to 100%.

| S-EPMC7745444 | biostudies-literature

Synthesis and Evaluation of Novel Ring-Strained Noncanonical Amino Acids for Residue-Specific Bioorthogonal Reactions in Living Cells.

Project description:Bioorthogonal reactions are ideally suited to selectively modify proteins in complex environments, even in vivo. Kinetics and product stability of these reactions are crucial parameters to evaluate their usefulness for specific applications. Strain promoted inverse electron demand Diels-Alder cycloadditions (SPIEDAC) between tetrazines and strained alkenes or alkynes are particularly popular, as they allow ultrafast labeling inside cells. In combination with genetic code expansion (GCE)-a method that allows to incorporate noncanonical amino acids (ncAAs) site-specifically into proteins in vivo. These reactions enable residue-specific fluorophore attachment to proteins in living mammalian cells. Several SPIEDAC capable ncAAs have been presented and studied under diverse conditions, revealing different instabilities ranging from educt decomposition to product loss due to β-elimination. To identify which compounds yield the best labeling inside living mammalian cells has frequently been difficult. In this study we present a) the synthesis of four new SPIEDAC reactive ncAAs that cannot undergo β-elimination and b) a fluorescence flow cytometry based FRET-assay to measure reaction kinetics inside living cells. Our results, which at first sight can be seen conflicting with some other studies, capture GCE-specific experimental conditions, such as long-term exposure of the ring-strained ncAA to living cells, that are not taken into account in other assays.

| S-EPMC8049044 | biostudies-literature

Novel Multitarget Hydroxamic Acids with a Natural Origin CAP Group against Alzheimer's Disease: Synthesis, Docking and Biological Evaluation.

Project description:Hydroxamic acids are one of the most promising and actively studied classes of chemical compounds in medicinal chemistry. In this study, we describe the directed synthesis and effects of HDAC6 inhibitors. Fragments of adamantane and natural terpenes camphane and fenchane, combined with linkers of various nature with an amide group, were used as the CAP groups. Accordingly, 11 original target compounds were developed, synthesized, and exposed to in vitro and in vivo biological evaluations, including in silico methods. In silico studies showed that all synthesized compounds were drug-like and could penetrate through the blood-brain barrier. According to the in vitro testing, hydroxamic acids 15 and 25, which effectively inhibited HDAC6 and exhibited anti-aggregation properties against β-amyloid peptides, were chosen as the most promising substances to study their neuroprotective activities in vivo. All in vivo studies were performed using 5xFAD transgenic mice simulating Alzheimer's disease. In these animals, the Novel Object Recognition and Morris Water Maze Test showed that the formation of hippocampus-dependent long-term episodic and spatial memory was deteriorated. Hydroxamic acid 15 restored normal memory functions to the level observed in control wild-type animals. Notably, this effect was precisely associated with the ability to restore lost cognitive functions, but not with the effect on motor and exploratory activities or on the level of anxiety in animals. Conclusively, hydroxamic acid 15 containing an adamantane fragment linked by an amide bond to a hydrocarbon linker is a possible potential multitarget agent against Alzheimer's disease.

| S-EPMC8623418 | biostudies-literature

Synthesis and antioxidant evaluation of enantiomerically pure bis-(1,2,3-triazolylmethyl)amino esters from modified ?-amino acids.

Project description:The efforts for synthesis of enantiomerically pure bis-(1,2,3-triazolylmethyl)amino esters 6 are reported in good yields from an in situ generated ?-azidomethyl ketone. Optimum experimental conditions were established for preparation of ?-halomethyl ketones 10 and ?-N,N-dipropargylamino esters 11, all derived from ?-amino acids. The starting materials reacted under conventional click chemistry conditions, revealing a specific reactivity of bromomethyl ketones over chloromethyl ketones. The antioxidant activity of compounds 6 was assayed by DPPH method. The compound 6c with an IC50 of 75.57 ± 1.74 ?g mL(-1) was the most active. Technically, this methodology allows the preparation of a combinatorial library of analogues with different structural characteristics depending on the nature of the modified ?-amino acids employed in the synthesis.

| S-EPMC4216715 | biostudies-literature

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility.

Project description:This article reports the synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase) and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS) to build the peptide segment (Phe-Arg-Gly-Asp or naphthAla-Phe-Arg-Gly-Asp with fully protected groups), and later, an amidation reaction in liquid phase connects these three parts together. The overall yield of these multiple step synthesis is about 34%. Besides exhibiting excellent solubility, these conjugates of saccharide-amino acids-nucleobase (SAN), like the previously reported conjugates of nucleobase-amino acids-saccharide (NAS) and nucleobase-saccharide-amino acids (NSA), are mammalian cell compatible.

| S-EPMC4222440 | biostudies-other

Mutant p53 regulates serine-glycine synthesis and essential amino acids intake

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-06 | GSE214494 | GEO

Synthesis of Diaryl Hydroxyl Dicarboxylic Acids from Amino Acids.

Project description:Herein we report a unique method for preparing diaryl hydroxyl dicarboxylic acids in a diastereospecific manner. The three-component reaction occurs between amino acid, aromatic aldehyde, and primary alcohol in alkaline solutions under microwave-assisted conditions. The dicarboxylic acids are isolated as sodium salts in high yields (up to 77%) by direct precipitation from the reaction solution. The experimental results suggest that the diastereospecificity originates from a [3,3]-sigmatropic rearrangement followed by a sodium-assisted hydride transfer. As further shown, the previously unreported dicarboxylic acids are easily turned into corresponding δ-lactones.

| S-EPMC7497638 | biostudies-literature

Direct Synthesis of ?-Thio Aromatic Acids from Aromatic Amino Acids.

Project description:Modified amino acids are useful synthetic components in both chemistry and biology. Here we describe a simple, scalable two-step procedure to generate ?-thio aromatic acids from aromatic amino acids with yields of up to 96%. Diazotization and ?-lactone mediated bromination efficiently form the ?-bromo acid with retention of configuration. Thiol substitution with mild reagents such as sodium hydrosulfide or sodium trithiocarbonate provides the inverted, free ?-thio acid. The mildly acidic soft nucleophile can then be utilized in many synthetic applications.

| S-EPMC6101259 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data