6384-18-5Relevant articles and documents
Oxovanadium(IV) complexes of salicyl-L-aspartic acid and salicylglycyl-L-aspartic acid
Jakusch, Tamas,Marcao, Susana,Rodrigues, Ligia,Correia, Isabel,Pessoa, Joao Costa,Kiss, Tamas
, p. 3072 - 3078 (2005)
The dipeptide and tripeptide analogues salicyl-L-aspartic acid (Sal-L-Asp) and salicylglycyl-L-aspartic acid (SalGly-L-Asp) were synthesized and their protonation and complex formation with VIVO2+ were studied in aqueous solution through the use of pH-potentiometry and spectroscopic (UV-Vis, CD and EPR) techniques. The phenolate terminus proved to be a good anchoring site to promote (i) the metal ion-induced deprotonation and subsequent coordination of the peptide amide group(s) in the pH range 4-5 for the dipeptide analogue, (ii) and in the pH range 5-6 in a very cooperative way for the tripeptide analogue. The results suggest that the presence of good anchoring donors on both sides of the amide groups is responsible for the cooperative deprotonation of the two amide-NH groups. The Royal Society of Chemistry 2005.
Experimental and theoretical evaluation on the conformational behavior of l-aspartic acid dimethyl ester and its N-acetylated derivative
Braga, Carolyne B.,Ducati, Lucas C.,Rittner, Roberto
, p. 18013 - 18024 (2015)
In this work the conformational preferences of l-aspartic acid dimethyl ester (AspOMe) and its N-acetylated derivative (AcAspOMe) were evaluated through spectroscopic data and theoretical calculations. Unlike amino acids, their corresponding amino ester derivatives do not exhibit a zwitterionic structure and are soluble in most organic solvents, enabling their studies in these media. Thus, the conformers of AspOMe and AcAspOMe were theoretically determined both in isolated phase and in solution (IEF-PCM model) at the ωB97X-D/aug-cc-pVTZ level. A joint analysis of the experimental and theoretical 3JHH coupling constants in several aprotic solvents allowed assigning the most stable conformers, showing excellent agreement between these approaches. Also, IR spectroscopy allowed us to obtain quantitative data on AcAspOMe conformer populations in different solvents. Natural bond orbital (NBO) analysis indicated that both steric and hyperconjugative contributions count in determining the relative conformer stabilities of these compounds. Intramolecular hydrogen bonding, characterized by Quantum Theory of Atoms in Molecules (QTAIM) and Non-Covalent Interactions (NCI) methodologies, represents only a secondary factor to drive the stabilities of AspOMe and AcAspOMe conformers. This journal is
Reaction of aspartic acid derivatives with Grignard reagents - Synthesis of γ,γ-disubstituted α- and β-amino-butyrolactones
Brinkmann, Thomas,Gilg, Alfred,Hamm, Andreas,Luesch, Hendrik,Morbach, Guido,Uzar, Horst C
, p. 3827 - 3836 (2000)
A series of γ,γ-dimethyl and γ,γ-diphenyl substituted α- and β-amino-butyrolactones have been prepared in enantiomerically pure form using L-aspartic acid as a chiral building block. For the final Grignard reaction the difference in chemical reactivity between the carboxyl groups of aspartic acid was increased or inverted by preparing the corresponding semiesters, diesters and anhydrides. The resulting hydroxyacids and hydroxyesters lactonised in most cases during work up. Thus, (2S)-2-ethoxycarbonylamino-succinic acid-4-methylester 1 reacted with methylmagnesium iodide to form (3S)-3-ethoxycarbonylamino-5,5-dimethyl-tetrahydrofuran-2-one 2b. Two interesting side products were obtained and were found to result from attack at the C-1 carboxylic acid rather than the C-4 carboxylic ester group leading to (3S)-3-ethoxycarbonylamino-4-oxo-pentanoic acid methylester 3 and (4S)-4-ethoxycarbonylamino-5,5-dimethyl-tetrahydrofuran-2-one 5a. Copyright (C) 2000 Elsevier Science Ltd.
Selective, Modular Probes for Thioredoxins Enabled by Rational Tuning of a Unique Disulfide Structure Motif
Becker, Katja,Busker, Sander,Felber, Jan G.,Maier, Martin S.,Poczka, Lena,Scholzen, Karoline,Theisen, Ulrike,Thorn-Seshold, Julia,Thorn-Seshold, Oliver,Zeisel, Lukas,Arnér, Elias S. J.,Brandst?dter, Christina
supporting information, p. 8791 - 8803 (2021/06/27)
Specialized cellular networks of oxidoreductases coordinate the dithiol/disulfide-exchange reactions that control metabolism, protein regulation, and redox homeostasis. For probes to be selective for redox enzymes and effector proteins (nM to μM concentrations), they must also be able to resist non-specific triggering by the ca. 50 mM background of non-catalytic cellular monothiols. However, no such selective reduction-sensing systems have yet been established. Here, we used rational structural design to independently vary thermodynamic and kinetic aspects of disulfide stability, creating a series of unusual disulfide reduction trigger units designed for stability to monothiols. We integrated the motifs into modular series of fluorogenic probes that release and activate an arbitrary chemical cargo upon reduction, and compared their performance to that of the literature-known disulfides. The probes were comprehensively screened for biological stability and selectivity against a range of redox effector proteins and enzymes. This design process delivered the first disulfide probes with excellent stability to monothiols yet high selectivity for the key redox-Active protein effector, thioredoxin. We anticipate that further applications of these novel disulfide triggers will deliver unique probes targeting cellular thioredoxins. We also anticipate that further tuning following this design paradigm will enable redox probes for other important dithiol-manifold redox proteins, that will be useful in revealing the hitherto hidden dynamics of endogenous cellular redox systems.
A Biocompatible Aspartic-Decorated Metal-Organic Framework with Tubular Motif Degradable under Physiological Conditions
Mon, Marta,Bruno, Rosaria,Lappano, Rosamaria,Maggiolini, Marcello,Di Donna, Leonardo,Ferrando Soria, Jesus,Armentano, Donatella,Pardo, Emilio
, p. 14221 - 14229 (2021/09/20)
Achieving a precise control of the final structure of metal-organic frameworks (MOFs) is necessary to obtain desired physical properties. Here, we describe how the use of a metalloligand design strategy and a judicious choice of ligands inspired from nature is a versatile approach to succeed in this challenging task. We report a new porous chiral MOF, with the formula Ca5II{CuII10[(S,S)-aspartamox]5}·160H2O (1), constructed from Cu2+and Ca2+ions and aspartic acid-decorated ligands, where biometal Cu2+ions are bridged by the carboxylate groups of aspartic acid moieties. The structure of MOF1reveals an infinite network of basket-like cages, built by 10 crystallographically distinct Cu(II) metal ions and five aspartamox ligands acting as bricks of a tubular motif, composed of seven basket-like cages each. The pillared hepta-packed cages generate pseudo-rhombohedral nanosized channels of ca. 0.7 and 0.4 nm along thebandacrystallographic axes. This intricate porous 3D network is anionic and chiral, each cage displaying receptor properties toward three-nuclear [Ca3(μ-H2O)4(H2O)17]6+entities. represents the first example of an extended porous structure based on essential biometals Cu2+and Ca2+ions together with aspartic acid as amino acid. shows good biocompatibility, making it a good candidate to be used as a drug carrier, and hydrolyzes in acid water. The hypothesis has been further supported by an adsorption experiment here reported, as a proof-of-principle study, using dopamine hydrochloride as a model drug to follow the encapsulation process. Results validate the potential ability of to act as a drug carrier. Thus, these make this MOF one of the few examples of biocompatible and degradable porous solid carriers for eventual release of drugs in the stomach stimulated by gastric low pH.
N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
Bárta, Pavel,Dole?al, Martin,Horá?ek, Ond?ej,Jand'Ourek, Ond?ej,Janou?ek, Ji?í,Juhás, Martin,Kone?ná, Klára,Ku?era, Radim,Ku?erová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Paterová, Pavla,Zitko, Jan
, (2020/04/09)
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
β-Hydroxy- A nd β-Aminophosphonate Acyclonucleosides as Potent Inhibitors of Plasmodium falciparum Growth
Cheviet, Thomas,Wein, Sharon,Bourchenin, Gabriel,Lagacherie, Manon,Périgaud, Christian,Cerdan, Rachel,Peyrottes, Suzanne
, p. 8069 - 8087 (2020/08/12)
Malaria is an infectious disease caused by a parasite of the genus Plasmodium, and the emergence of parasites resistant to all current antimalarial drugs highlights the urgency of having new classes of molecules. We developed an effective method for the synthesis of a series of β-modified acyclonucleoside phosphonate (ANP) derivatives, using commercially available and inexpensive materials (i.e., aspartic acid and purine heterocycles). Their biological evaluation in cell culture experiments and SAR revealed that the compounds' effectiveness depends on the presence of a hydroxyl group, the chain length (four carbons), and the nature of the nucleobase (guanine). The most active derivative inhibits the growth of Plasmodium falcIParum in vitro in the nanomolar range (IC50 = 74 nM) with high selectivity index (SI > 1350). This compound also showed remarkable in vivo activity in P. berghei-infected mice (ED50 ～0.5 mg/kg) when administered by the IP route and is, although less efficient, still active via the oral route. It is the first ANP derivative with such potent antimalarial activity and therefore has considerable potential for development as a new antimalarial drug.
Urethanes synthesis from oxamic acids under electrochemical conditions
Ogbu, Ikechukwu Martin,Lusseau, Jonathan,Kurtay, Gülbin,Robert, Frédéric,Landais, Yannick
supporting information, p. 12226 - 12229 (2020/10/26)
Urethane synthesis via oxidative decarboxylation of oxamic acids under mild electrochemical conditions is reported. This simple phosgene-free route to urethanes involves an in situ generation of isocyanates by anodic oxidation of oxamic acids in an alcoholic medium. The reaction is applicable to a wide range of oxamic acids, including chiral ones, and alcohols furnishing the desired urethanes in a one-pot process without the use of a chemical oxidant.
Synthesis of Nitro-Aryl Functionalised 4-Amino-1,8-Naphthalimides and Their Evaluation as Fluorescent Hypoxia Sensors
Adair, Liam D.,Trinh, Natalie,Vérité, Pauline M.,Jacquemin, Denis,Jolliffe, Katrina A.,New, Elizabeth J.
supporting information, p. 10064 - 10071 (2020/07/04)
Fluorescent sensors are a vital research tool, enabling the study of intricate cellular processes in a sensitive manner. The design and synthesis of responsive and targeted probes is necessary to allow such processes to be interrogated in the cellular environment. This remains a challenge, and requires methods for functionalisation of fluorophores with multiple appendages for sensing and targeting groups. Methods to synthesise more structurally complex derivatives of fluorophores will expand their potential scope. Most known 4-amino-1,8-naphthalimides are only functionalised at imide and 4-positions, and structural modifications at additional positions will increase the breadth of their utility as responsive sensors. In this work, methods for the incorporation of a hypoxia sensing group to 4-amino-1,8-naphthalimide were evaluated. An intermediate was developed that allowed us to incorporate a sensing group, targeting group, and ICT donor to the naphthalimide core in a modular fashion. Synthetic strategies for attaching the hypoxia sensing group and how they affected the fluorescence of the naphthalimide were evaluated by photophysical characterisation and time-dependent density functional theory. An extracellular hypoxia probe was then rationally designed that could selectively image the hypoxic and necrotic region of tumour spheroids. Our results demonstrate the versatility of the naphthalimide scaffold and expand its utility. This approach to probe design will enable the flexible, efficient generation of selective, targeted fluorescent sensors for various biological purposes.
Visible-light mediated carbamoyl radical addition to heteroarenes
Jatoi, Ashique Hussain,Pawar, Govind Goroba,Robert, Frédéric,Landais, Yannick
supporting information, p. 466 - 469 (2019/01/10)
The generation of carbamoyl radicals, followed by their addition to heteroarenes, was performed under mild conditions through a metal-free photocatalyzed decarboxylation of oxamic acids. The process has been applied to the carbamoylation of heteroaromatic bases using α-aminoacid-derived oxamic acids, leading to the corresponding amides without racemization.
