1080-06-4Relevant articles and documents
A dinuclear biomimetic Cu complex derived from l-histidine: synthesis and stereoselective oxidations
Perrone, Maria L.,Salvadeo, Elena,Lo Presti, Eliana,Pasotti, Luca,Monzani, Enrico,Santagostini, Laura,Casella, Luigi
, p. 4018 - 4029 (2017)
A dinuclear copper(ii) complex derived from the chiral N6 ligand (2S,2′S)-N,N′-(ethane-1,2-diyl)bis(2-((1-methyl-1H-imidazol-4-ylmethyl)-amino)-3-(1-trityl-1H-imidazol-4-yl)propanamide) (EHI) was synthesized and studied as a catalyst in stereoselective oxidation reactions. The ligand contains two sets of tridentate binding units, each of them giving rise to a coordination set consisting of a pair of 5- and 6-membered chelate rings, connected by an ethanediamide linker. Stereoselectivity effects were studied in the oxidations of a series of chiral l/d biogenic catechols and the pair of l/d-tyrosine methyl esters, in this case as their phenolate salts. The oxidation of β-naphthol has also been studied as a model monooxygenase reaction. The catechol oxidation was investigated in a range of substrate concentrations at slightly acidic pH and exhibited a marked dependence on the concentration of the [Cu2EHI]4+ complex. This behavior has been interpreted in terms of an equilibrium between a monomeric and a dimeric form of the catalyst. Binding studies of l- and d-tyrosine were performed as a support for the interpretation of the stereoselectivity effects observed in the reactions. In general, [Cu2EHI]4+ exhibits a binding preference for the l- rather than the d-enantiomer of the substrates, but it appears that in the catecholase reaction the oxidation of the d-isomer occurs at a faster rate than for the l counterpart. The same type of enantio-discriminating behavior is observed in the oxidation of l-/d-tyrosine methyl esters. In this case the reaction produces a complex mixture of products; the main product consisting of a trimeric compound, likely formed by radical coupling reactions, has been isolated and characterized. The oxidation of β-naphthol yields an additional product of the expected quinone but labeling experiments with 18-O2 show no oxygen incorporation into the product, confirming that the oxidation likely proceeds through a radical mechanism.
Stabilized 111In-labeled sCCK8 analogues for targeting CCK2-receptor positive tumors: Synthesis and evaluation
Roosenburg, Susan,Laverman, Peter,Joosten, Lieke,Eek, Annemarie,Oyen, Wim J. G.,De Jong, Marion,Rutjes, Floris P. J. T.,Van Delft, Floris L.,Boerman, Otto C.
, p. 663 - 670 (2010)
Radiolabeled cholecystokinin-8 (CCK8) peptide analogues can be used for peptide receptor radionuclide imaging and therapy for tumors expressing CCK2/gastrin receptors. Earlier findings indicated that sulfated CCK8 (sCCK8, Asp-Tyr(OSO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) may have better characteristics for peptide receptor radionuclide therapy (PRRT) than gastrin analogues. However, sCCK8 contains an easily hydrolyzable sulfated tyrosine residue and two methionine residues which are prone to oxidation. Here, we describe the synthesis of stabilized sCCK8 analogues, resistant to hydrolysis and oxidation. Hydrolytic stability was achieved by replacement of the Tyr(OSO3H) moiety by a robust isosteric sulfonate, Phe(p-CH 2SO3H). Replacement of methionine by norleucine (Nle) or homopropargylglycine (HPG) avoided undesired oxidation side-reactions. The phenylalanine analogue Phe(p-CH2SO3H) of l-tyrosine, synthesized by a modification of known synthetic routes, was incorporated in three peptides: sCCK8[Phe2(p-CH2SO3H),Met 3,6], sCCK8[Phe2(p-CH2SO3H),Nle 3,6], and sCCK8[Phe2(p-CH2SO 3H),HPG3,6]. All peptides were N-terminally conjugated with the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-N,N,N,N- tetraacetic acid) and radiolabeled with In-111. In vitro binding assays on CCK2R-expressing HEK293 cells revealed that all three peptides showed specific binding and receptor-mediated internalization, with binding affinity values (IC50) in the nanomolar range. In vitro oxidation studies demonstrated that peptides with Nle or HPG indeed were resistant to oxidation. In vivo targeting studies in mice with AR42J tumors showed that tumor uptake was highest for 111In-DOTA-sCCK8 and 111In-DOTA- sCCK8[Phe2(p-CH2SO3H),Nle3,6] (4.78 ± 0.64 and 4.54 ± 1.15%ID/g, respectively, 2 h p.i.). The peptide with the methionine residues replaced by norleucine (111In-DOTA- sCCK8[Phe2(p-CH2SO3H), Nle3,6]) showed promising in vivo characteristics and will be further investigated for radionuclide imaging and therapy of CCK2R-expressing tumors.
An auxin-tyrosine derivative based biocompatible supergelator: A template for fabrication of nanoparticles for sustained release of model drugs
Tiwari, Priyanka,Basu, Anindya,Sahu, Sonu,Gound, Sadhna,Christman, Ryann M.,Tiwari, Amit K.,Trivedi, Piyush,DuttKonar, Anita
, p. 4915 - 4922 (2018)
Bioinspired self-assembling peptides serve as powerful building blocks in the manufacturing of nanomaterials with tailored features. Inspired by the supergelating ability of naphthyl-Phe-OH (hydrogelator I), we synthesized naphthyl-Tyr-OH (hydrogelator II) and naphthyl-Trp-OH (hydrogelator III) with the objective of exploring the propensities of the phenolic OH of Tyr and the NH of the indole for controlling the gelation process. However, our experimental investigation reveals that hydrogelator II, containing Tyr as the aromatic core, shows an excellent gelation ability. But the Trp analogue fails to do so under similar conditions. To validate our results we performed MD simulation in an aqueous environment which significantly justifies that hydrogelator II exhibits a better hydrogelation ability than hydrogelators I and III. The characterisation of hydrogelator II was then performed in detail using various analytical and microscopic techniques and its biocompatibility was tested using an MTT assay. To examine the potentiality of hydrogelator II in drug delivery we developed hydrogel nanoparticles (HNPs) using the concept of self-assembly entirely governed by an ecofriendly approach i.e. weak interactions (like H-bonding, π-π and hydrophobic interactions). Our hydrogel nanoparticles display good release kinetics of the model drugs 5-fluorouracil and curcumin from the hydrogel matrix depending on their chemical structure, molecular weight and hydrophobicity. Thus our research shows that the choice of the core residue has a profound impact on the self-assembly process and thus on the gelation properties. Moreover, nanoparticles generated from our novel biocompatible hydrogelator II hold promise for future drug delivery applications.
Synthesis, characterization and in vitro antimicrobial and biodegradability study of pseudo-poly(amino acid)s derived from N,N′-(pyromellitoyl)-bis- l-tyrosine dimethyl ester as a chiral bioactive diphenolic monomer
Mallakpour, Shadpour,Tirgir, Farhang,Sabzalian, Mohammad R.
, p. 611 - 621 (2011)
In this investigation N,N′-(pyromellitoyl)-bis-l-tyrosine dimethyl ester (7) as a chiral bioactive diphenolic monomer was prepared in three steps. The aim of this work was to obtain novel optically and biologically active pseudo-poly(amino acid)s (PAA)s that are more soluble in common organic solvents while maintaining their high thermal stability. Thus, several new, highly soluble, thermally stable, optically active and biodegradable PAAs containing different amino acid moieties in the main chain were prepared with moderate molecular weights via direct polycondensation using tosyl chloride, pyridine and N,N′-dimethylformamide as a condensing agent. The resulting novel polymers were characterized with FT-IR, 1H-NMR, elemental and thermogravimetric analysis techniques. In addition, in vitro toxicity and biodegradability behavior of the diphenolic monomer 7, different synthetic diacids (3a-3e) and obtained PAAs, which were investigated in culture media, showed that the synthesized compounds and polymers derived from them are biologically active and biodegradable under a natural environment.
Fabrication of biodegradable poly(ester-amide)s based on tyrosine natural amino acid
Abdolmaleki, Amir,Mallakpour, Shadpour,Borandeh, Sedigheh,Sabzalian, Mohammad R.
, p. 1997 - 2007 (2012)
N,N'-Bis[2-(methyl-3-(4-hydroxyphenyl)propanoate)] isophthaldiamide (5), a novel diol monomer containing chiral group, was prepared by the reaction of S-tyrosine methyl ester (3) with isophthaloyl dichloride (4a). A new family of optically active and potentially biodegradable poly(ester-amide)s (PEAs) based on tyrosine amino acid were prepared by the polycondensation reaction of diol monomer 5 with several aromatic diacid chlorides. The resulting new polymers were obtained in good yields with inherent viscosities ranging between 0.25 and 0.42 dL/g and are soluble in polar aprotic solvents. They showed good thermal stability and high optical purity. The synthetic compounds were characterized and studied by FT-IR, 1H-NMR, specific rotation, elemental and thermogravimetric analysis (TGA) techniques and typical ones by 13C-NMR, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM) analysis. Soil burial test of the diphenolic monomer 5, and obtained PEA6a, and soil enzymatic assay showed that the synthesized diol and its polymer are biologically active and probably biodegradable in soil environment. Springer-Verlag 2011.
New 1,4-anthracene-9,10-dione derivatives as potential anticancer agents
Zagotto,Supino,Favini,Moro,Palumbo
, p. 1 - 5 (2000)
The amino-substituted anthracene-9,10-dione (9,10-anthraquinone) derivatives represent one of the most important classes of potential anticancer agents. To better understand the basic rules governing DNA sequence specificity, we have recently synthesized a new class of d- and l- aminoacyl-anthraquinone derivatives. We have tested these new compounds as cytotoxic agents, and we have correlated their activity with the configuration of the chiral aminoacyl moiety. Molecular modeling studies have been performed to compare the test drugs in terms of steric overlapping. (C) 2000 Elsevier Science S.A.
Differentiation of natural and synthetic phenylalanine and tyrosine through natural abundance 2H nuclear magnetic resonance
Brenna, Elisabetta,Fronza, Giovanni,Fuganti, Claudio,Pinciroli, Matteo
, p. 4866 - 4872 (2003)
The natural abundance deuterium NMR characterization of samples of the amino acids tyrosine (1) and phenylalanine (2), examined as the acetylated methyl esters 4 and 6, has been performed with the aim to identify by these means the contribution in animals of the hydroxylation of the diet L-phenylalanine (2) to the formation of L-tyrosine (1), a feature previously revealed on the same samples through the determination of the phenolic δ18O values. The study, which includes also the NMR examination of benzoic acid (5) from 2 and of tyrosol (7) from 1, substantially fails in providing the required information because the mode of deuterium labeling of tyrosine samples of different origins is quite similar but indicates a dramatic difference in the deuterium labeling pattern of the two amino acids 1 and 2. The most relevant variation is with regard to the deuterium enrichments at the CH2 and CH positions, which are inverted in the two amino acids of natural derivation. Moreover, whereas the diastereotopic benzylic hydrogen atoms of L-tyrosine (1) appear to be equally deuterium enriched, in L-phenylalanine (2) the (D/H)3R > (D/H)3S. Similarly, benzoic acid (5) shows separate signals for the aromatic deuterium nuclei, which are quite indicative of the natural or synthetic derivation. The mode of deuterium labeling of the side chain of 1 and 2 is tentatively correlated to the different origins of the two amino acids, natural from animal sources for L-tyrosine and biotechnological probably from genetically modified microorganisms for L-phenylalanine.
New Type of Aldol Condensations Catalyzed by Metal(II) Complexes of α-Amino Acid Esters and that with Cyclodextrin System
Watanabe, Ken-ichi,Yamada, Yoichi,Goto, Katsuhisa
, p. 1401 - 1406 (1985)
The aldol condensation of p-nitrobenzaldehyde with acetone catalyzed by metal ccomplexes of α-amino acid esters proceeded under mild and neutral conditions to afford an enantiomeric excess aldol-type products, 4-hydroxy-4-(4-nitrophenyl)-2-butanone, along with same dehydrated products without any by-product.The most effective catalyst system was a zinc(II) complex of the tyrosine ethyl ester, Zn(II)-(TyrOEt)2 in MeOH.Complexes of the second-row transition metals were inadeguate for the reactions.Reactions at 30-40 deg C for 24 h were fovorable regarding the asymmetric induction.An H2O solvent was the best for aldol-type product formation without asymmetric induction.An assistand effect of cyclodextrins(especially, β-CD) on the catalysis of the Zn(II)-TyrOEt complex were thought to be observed.
Synthesis of d,l-amino acid derivatives bearing a thiol at the β-position and their enzymatic optical resolution
Morishita, Yasuhito,Kaino, Tomoka,Okamoto, Ryo,Izumi, Masayuki,Kajihara, Yasuhiro
, p. 6565 - 6568 (2015)
Amino acids bearing a thiol group at the β-position are useful for native chemical ligation. Phenylalanine and tyrosine derivatives bearing a thiol group at the β-position were synthesized. Racemic phenylalanine and tyrosine were selected as starting materials and were introduced a bromo atom at the β-position by photoreaction. Subsequent substitution reaction of the bromo atom with p-methoxybenzylmercaptan yielded the corresponding amino acids bearing a thiol group at the β-position. Enzymatic optical resolution using l-aminoacylase and subsequent chemical conversion gave the corresponding optically pure l- and d-phenylalanine and tyrosine derivatives bearing a thiol group at the β-position.
Optimisation of conditions for O-benzyl and N-benzyloxycarbonyl protecting group removal using an automated flow hydrogenator
Knudsen, Kristian Rahbek,Holden, John,Ley, Steven V.,Ladlow, Mark
, p. 535 - 538 (2007)
A versatile, fully automated flow hydrogenator has been developed that is able to perform sequential flow optimisation experiments, flow library hydrogenation, or iterative scale-up hydrogenation. The behaviour of a palladium catalyst in effecting removal of O-benzyl and N-benzyloxycarbonyl protecting groups has been investigated. Significant observations relating to maintaining optimal throughput are reported. A small library of peptidic derivatives has been deprotected in high yield and purity.
