- Synthesis of Imidazole and Histidine-Derived Cross-Linkers as Analogues of GOLD and Desmosine
-
Amino acid derivatives with a central cationic heterocyclic core (e.g., imidazolium) are biologically relevant cross-linkers of proteins and advanced glycation end (AGE) products. Here, imidazolium-containing cross-linkers were synthesized from imidazole or histidine by N-alkylation employing aspartate- and glutamate-derived mesylates as key step. Biological investigations were carried out to probe the biocompatibility of these compounds.
- Sch?del, Nicole,Icik, Esra,Martini, Maike,Altevogt, Luca,Ramming, Isabell,Greulich, Andreas,Baro, Angelika,Bilitewski, Ursula,Laschat, Sabine
-
supporting information
p. 2260 - 2268
(2021/03/04)
-
- N(?)-2-Naphthylmethoxymethyl-Protected Histidines: Scalable, Racemization-Free Building Blocks for Peptide Synthesis
-
Histidine (His) racemizes with relative ease during peptide synthesis. One strategy to suppress this racemization is to protect the nitrogen atom of the imidazole moiety in His with a suitable protecting group. Among the numerous protecting groups that have already been tested, the p-methoxybenzyloxymethyl (PMBOM) group on the ?-nitrogen atom effectively suppresses the racemization. However, a large-scale synthesis of N(?)-PMBOM-protected derivatives has hitherto been hampered by the requirement of a freshly prepared unstable reagent. Herein we report the synthesis of N(?)-2-naphthylmethoxymethyl (NAPOM)-protected His derivatives, which can be prepared on a gram scale and do not suffer from the aforementioned instability problems. Furthermore, these NAPOM-protected His derivatives suppress the racemization in Boc- A nd Fmoc-based peptide synthesis.
- Torikai, Kohei,Watanabe, Louis A.,Yanagimoto, Ryota
-
p. 448 - 453
(2020/04/08)
-
- Carnosine protects cardiac myocytes against lipid peroxidation products
-
Endogenous histidyl dipeptides such as carnosine (β-alanine-l-histidine) form conjugates with lipid peroxidation products such as 4-hydroxy-trans-2-nonenal (HNE and acrolein), chelate metals, and protect against myocardial ischemic injury. Nevertheless, it is unclear whether these peptides protect against cardiac injury by directly reacting with lipid peroxidation products. Hence, to examine whether changes in the structure of carnosine could affect its aldehyde reactivity and metal chelating ability, we synthesized methylated analogs of carnosine, balenine (β-alanine-Nτ-methylhistidine) and dimethyl balenine (DMB), and measured their aldehyde reactivity and metal chelating properties. We found that methylation of Nτ residue of imidazole ring (balenine) or trimethylation of carnosine backbone at Nτ residue of imidazole ring and terminal amine group dimethyl balenine (DMB) abolishes the ability of these peptides to react with HNE. Incubation of balenine with acrolein resulted in the formation of single product (m/z 297), whereas DMB did not react with acrolein. In comparison with carnosine, balenine exhibited moderate acrolein quenching capacity. The Fe2+ chelating ability of balenine was higher than that of carnosine, whereas DMB lacked chelating capacity. Pretreatment of cardiac myocytes with carnosine increased the mean lifetime of myocytes superfused with HNE or acrolein compared with balenine or DMB. Collectively, these results suggest that carnosine protects cardiac myocytes against HNE and acrolein toxicity by directly reacting with these aldehydes. This reaction involves both the amino group of β-alanyl residue and the imidazole residue of l-histidine. Methylation of these sites prevents or abolishes the aldehyde reactivity of carnosine, alters its metal-chelating property, and diminishes its ability to prevent electrophilic injury.
- Zhao, Jingjing,Posa, Dheeraj Kumar,Kumar, Vijay,Hoetker, David,Kumar, Amit,Ganesan, Smirthy,Riggs, Daniel W.,Bhatnagar, Aruni,Wempe, Michael F.,Baba, Shahid P.
-
p. 123 - 138
(2018/11/23)
-
- Development of an LC–tandem mass spectrometry method for the quantitative analysis of hercynine in human whole blood
-
Given that the peculiar redox behavior of ergothioneine involves a rapid regeneration process, the measurement of its precursor and redox metabolite hercynine could be particularly useful in assessing its role in oxidative stress or other biological processes. Thus, a LC-MS/MS method for the determination of hercynine concentrations in whole blood was developed. After lysis of red blood cells by cold water, samples were filtered on micro concentrators at a controlled temperature of 4 ?C. The clear filtered fluid was then treated with diethylpyrocarbonate to derivatize hercynine for the analysis by LC-MS/MS. The derivatized analyte was isocratically separated as a carbethoxy derivative on a C18 column with a mobile phase of an aqueous 0.1% v/v formic acid and acetonitrile (95:5). Effluents were monitored by MRM transitions at m/z 270.28→95 and 273.21→95 for hercynine and its deuterated counterpart, respectively. No cross-talk between MRM transitions was observed and a good linearity was found within a range of 35–1120 nmol/L. The LOD and LOQ were, respectively, 10.30 and 31.21 nmol/L with an intraday and intermediate precision below 7%. The average hercynine concentration in whole blood from 30 healthy male volunteers (aged 77 ± 12 years) was 178.5 ± 118.1 nmol/L. Overall, the method is easy to perform, allowing a rapid and accurate assessment of whole blood concentrations of hercynine.
- Sotgia, Salvatore,Murphy, Rhys B.,Zinellu, Angelo,Elliot, David,Paliogiannis, Panagiotis,Pinna, Gerard Aimè,Carru, Ciriaco,Mangoni, Arduino A.
-
supporting information
(2019/01/03)
-
- A novel high-capacity immunoadsorbent with PAMAM dendritic spacer arms by click chemistry
-
Polyamidoamine (PAMAM) dendrimers, bearing multiple peripheral end groups that can be used as clickable modules, make it possible to bind a large number of small-molecule ligands via click chemistry to prepare high-capacity immunoadsorbents. Thus, an immunoadsorbent with PAMAM dendritic spacer arms possessing pseudo-biospecific affinity for IgG from human plasma, Sep-PAMAM-AA, was designed and prepared by click chemistry using sepharose gel as a support and the amino acids His, Phe and Trp as ligands; two sepharose-based control samples, Sep-triazole-His and Sep-PA, with linear spacer arms were prepared using l-histidine and protein A as ligands, respectively. The ligand density and IgG adsorption performance of Sep-PAMAM-AA from human plasma were measured and evaluated. The influences of the structure and generation number of the PAMAM spacer arms on the performances of the products were also investigated. The results indicate that the immunoadsorbent with PAMAM G3 as a spacer arm and His as a ligand, Sep-G3-His, is the best among the prepared immunoadsorbents. Its ligand density reaches 1.58 mmol g?1 sepharose gel, almost 5-fold higher than that of Sep-triazole-His; its IgG adsorption capacity is 28.43 mg g?1, which is higher than those of Sep-triazole-His and Sep-PA. Moreover, Sep-G3-His exhibits a relatively low level of non-specific adsorption, which indicates that the immunoadsorbents with PAMAM as a spacer arm and His as a ligand are expected to have great application prospects in the field of blood purification.
- Hu, Xiaoyan,Li, Guangji,Lin, Yinlei
-
p. 15726 - 15732
(2018/10/04)
-
- Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)
-
The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Additionally, the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer.
- Chien, Huan-Chieh,Colas, Claire,Finke, Karissa,Springer, Seth,Stoner, Laura,Zur, Arik A.,Venteicher, Brooklynn,Campbell, Jerome,Hall, Colton,Flint, Andrew,Augustyn, Evan,Hernandez, Christopher,Heeren, Nathan,Hansen, Logan,Anthony, Abby,Bauer, Justine,Fotiadis, Dimitrios,Schlessinger, Avner,Giacomini, Kathleen M.,Thomas, Allen A.
-
supporting information
p. 7358 - 7373
(2018/08/06)
-
- An Amphotericin B derivative equally potent to Amphotericin B and with increased safety
-
Amphotericin B is the most potent antimycotic known to date. However due to its large collateral toxicity, its use, although long standing, had been limited. Many attempts have been made to produce derivatives with reduced collateral damage. The molecular mechanism of polyene has also been closely studied for this purpose and understanding it would contribute to the development of safe derivatives. Our study examined polyene action, including chemical synthesis, electrophysiology, pharmacology, toxicology and molecular dynamics. The results were used to support a novel Amphotericin B derivative with increased selectivity: L-histidine methyl ester of Amphotericin B. We found that this derivative has the same form of action as Amphotericin B, i.e. pore formation in the cell membrane. Its reduced dimerization in solution, when compared to Amphotericin B, is at least partially responsible for its increased selectivity. Here we also present the results of preclinical tests, which show that the derivative is just as potent as Amphotericin B and has increased safety.
- Antillón, Armando,De Vries, Alexander H.,Espinosa-Caballero, Marcel,Falcón-González, José Marcos,Flores Romero, David,González-Damián, Javier,Jiménez-Montejo, Fabiola Eloísa,León-Buitimea, Angel,López-Ortiz, Manuel,Maga?a, Ricardo,Marrink, Siewert J.,Morales-Nava, Rosmarbel,Periole, Xavier,Reyes-Esparza, Jorge,Rodríguez Lozada, Josué,Santiago-Angelino, Tania Minerva,Vargas González, María Cristina,Regla, Ignacio,Carrillo-Tripp, Mauricio,Fernández-Zertuche, Mario,Rodríguez-Fragoso, Lourdes,Ortega-Blake, Iván
-
-
- Concise Synthesis of Anserine: Efficient Solvent Tuning in Asymmetric Hydrogenation Reaction
-
A concise synthesis of anserine and related compounds was accomplished by Et-DuPhos-Rh-catalyzed asymmetric hydrogenation of dehydrohistidine derivatives in 2,2,2-trifluoroethanol, which played a key role in improving the yield and selectivity.
- Yamashita, Megumi,Shimizu, Keita,Koizumi, Yasuaki,Wakimoto, Toshiyuki,Hamashima, Yoshitaka,Asakawa, Tomohiro,Inai, Makoto,Kan, Toshiyuki
-
supporting information
p. 2734 - 2736
(2016/11/30)
-
- Synthesis and antimicrobial activities of His(2-aryl)-Arg and Trp-His(2-aryl) classes of dipeptidomimetics
-
In this communication, we report the design, synthesis and in vitro antimicrobial activity of ultra short peptidomimetics. Besides producing promising antibacterial activities against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), the dipeptidomimetics exhibited high antifungal activity against C. neoformans with IC50 values in the range of 0.16-19 μg mL-1. The most potent analogs exhibited 4-fold higher activity than the currently used drug amphotericin B, with no apparent cytotoxicity in a panel of mammalian cell lines. This journal is the Partner Organisations 2014.
- Mahindra, Amit,Sharma, Krishna K.,Rathore, Dinesh,Khan, Shabana. I.,Jacob, Melissa R.,Jain, Rahul
-
supporting information
p. 671 - 676
(2014/05/06)
-
- Synthetically modified l-histidine-rich peptidomimetics exhibit potent activity against Cryptococcus neoformans
-
We describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified l-histidine. Two series of tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position of l-histidine and at the N- and C-terminus. The data indicates that peptides (5f, 6f, 9f and 10f) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of all with IC50 and MFC values of 0.60 and 0.63 μg/mL, respectively, compared to the commercial drug amphotericin B (IC50 = 0.69 and MFC = 1.25 μg/mL). The selectivity of these peptides to microbial pathogen was examined by a tryptophan fluorescence quenching study and transmission electron microscopy. These studies indicate that the peptides plausibly interact with the mimic membrane of pathogen by direct insertion, and results in disruption of membrane of pathogen.
- Jain, Rahul,Mahindra, Amit,Bagra, Nitin,Wangoo, Nishima,Jain, Rohan,Khan, Shabana I.,Jacob, Melissa R.
-
supporting information
p. 3150 - 3154
(2014/06/24)
-
- Synthetically modified l-histidine-rich peptidomimetics exhibit potent activity against Cryptococcus neoformans
-
We describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified l-histidine. Two series of tripeptidomimetics were synthesized by varying lipophilicity at the C-2 position of l-histidine and at the N- and C-terminus. The data indicates that peptides (5f, 6f, 9f and 10f) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of Cryptococcus neoformans. Peptide 6f is the most potent of all with IC50 and MFC values of 0.60 and 0.63 μg/mL, respectively, compared to the commercial drug amphotericin B (IC50 = 0.69 and MFC = 1.25 μg/mL). The selectivity of these peptides to microbial pathogen was examined by a tryptophan fluorescence quenching study and transmission electron microscopy. These studies indicate that the peptides plausibly interact with the mimic membrane of pathogen by direct insertion, and results in disruption of membrane of pathogen.
- Mahindra, Amit,Bagra, Nitin,Wangoo, Nishima,Jain, Rohan,Khan, Shabana I.,Jacob, Melissa R.,Jain, Rahul
-
supporting information
p. 3150 - 3154
(2015/02/19)
-
- Histidine-functionalized water-soluble nanoparticles for biomimetic nucleophilic/general-base catalysis under acidic conditions
-
Cross-linking the micelles of 4-dodecyloxybenzyltripropargylammonium bromide by 1,4-diazidobutane-2,3-diol in the presence of azide-functionalized imidazole derivatives yielded surface-cross-linked micelles (SCMs) with imidazole groups on the surface. The
- Chadha, Geetika,Zhao, Yan
-
supporting information
p. 6849 - 6855
(2013/10/01)
-
- Predicting the physicochemical profile of diastereoisomeric histidine-containing dipeptides by property space analysis
-
Objectives: This study aimed at measuring the lipophilicity and ionization constants of diastereoisomeric dipeptides, interpreting them in terms of conformational behavior, and developing statistical models to predict them. Methods: A series of 20 dipeptides of general structure NH2-L-X-(L or D)-His-OMe was designed and synthetized. Their experimental ionization constants (pK1, pK2 and pK3) and lipophilicity parameters (log PN and log D7.4) were measured by potentiometry. Molecular modeling in three media (vacuum, water, and chloroform) was used to explore and sample their conformational space, and for each stored conformer to calculate their radius of gyration, virtual log P (preferably written as log PMLP, meaning obtained by the molecular lipophilicity potential (MLP) method) and polar surface area (PSA). Means and ranges were calculated for these properties, as was their sensitivity (i.e., the ratio between property range and number of rotatable bonds). Results: Marked differences between diastereoisomers were seen in their experimental ionization constants and lipophilicity parameters. These differences are explained by molecular flexibility, configuration-dependent differences in intramolecular interactions, and accessibility of functional groups. Multiple linear equations correlated experimental lipophilicity parameters and ionization constants with PSA range and other calculated parameters. Conclusion: This study documents the differences in lipophilicity and ionization constants between diastereoisomeric dipeptides. Such configuration-dependent differences are shown to depend markedly on differences in conformational behavior and to be amenable to multiple linear regression.
- Vistoli, Giulio,Straniero, Valentina,Pedretti, Alessandro,Fumagalli, Laura,Bolchi, Cristiano,Pallavicini, Marco,Valoti, Ermanno,Testa, Bernard
-
experimental part
p. 566 - 576
(2012/08/29)
-
- The reaction of optically active α-aminocarboxylic acid hydrazides with triethyl orthoesters
-
New derivatives of 2-(1-amino-1-phenylmethyl)-1,3,4-oxadiazole and 1,2,4-triazin-6-one were synthesised in the reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The electronic and steric effects of substituents at the α position influencing the formation of five- or six-membered products are discussed.
- Kudelko, Agnieszka,Zieliński, Wojciech,Ejsmont, Krzysztof
-
experimental part
p. 7838 - 7845
(2011/10/12)
-
- SAR and molecular mechanism study of novel acylhydrazone compounds targeting HIV-1 CA
-
We synthesized a series of acylhydrazone compounds bearing naturally occurring amino acids' side chains as HIV assembly inhibitors. Biological evaluation indicated that the compounds had anti-SIV and capsid assembly inhibitory activities. The structure-activity relationship (SAR) study showed that compounds bearing proper aromatic side chains had potential antiviral activities. The molecular modeling experiments revealed the molecular mechanism that they could bind to CA in the same manner as CAP-1 and occupy two more grooves.
- Jin, Yinxue,Tan, Zhiwu,He, Meizi,Tian, Baohe,Tang, Shixing,Hewlett, Indira,Yang, Ming
-
experimental part
p. 2135 - 2140
(2010/06/12)
-
- Hit to lead studies on (hetero)arylpyrimidines-Agonists of the canonical Wnt-β-catenin cellular messaging system
-
A series of (hetero)arylpyrimidines agonists of the Wnt-β-catenin cellular messaging system have been prepared. These compounds show activity in U2OS cells transfected with Wnt-3a, TCF-luciferase, Dkk-1 and tk-Renilla. Selected compounds show minimal GSK-3β inhibition indicating that the Wnt-β-catenin agonism activity most likely comes from interaction at Wnt-3a/Dkk-1. Two examples 1 and 25 show in vivo osteogenic activity in a mouse calvaria model. One example 1 is shown to activate non-phosphorylated β-catenin formation in bone.
- Gilbert, Adam M.,Bursavich, Matthew G.,Alon, Nippa,Bhat, Bheem M.,Bex, Frederick J.,Cain, Michael,Coleburn, Valerie,Gironda, Virginia,Green, Paula,Hauze, Diane B.,Kharode, Yogendra,Krishnamurthy, Girija,Kirisits, Matthew,Lam, Ho-Sun,Liu, Yao-Bin,Lombardi, Sabrina,Matteo, Jeanne,Murrills, Richard,Robinson, John A.,Selim, Sally,Sharp, Michael,Unwalla, Raymond,Varadarajan, Usha,Zhao, Weiguang,Yaworsky, Paul J.
-
scheme or table
p. 366 - 370
(2010/04/06)
-
- Discovery of Trp-His and His-Arg analogues as new structural classes of short antimicrobial peptides
-
Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. In search of short antimicrobial peptides, which represent a possible alternative for lead structures to fight antibiotic
- Sharma, Rohit K.,Reddy, Ravi P.,Tegge, Werner,Jain, Rahul
-
scheme or table
p. 7421 - 7431
(2010/06/11)
-
- PROCESS FOR THE SYNTHESIS OF L-(+)-ERGOTHIONEINE
-
This invention relates to a novel process for the preparation of optically pure L-(+)-ergothioneine. The process for the chemical synthesis of L-ergothioneine comprises steps which consist of reacting L-histidine alkyl ester with an acid halide, chloroformate or pyrocarbonate in the presence of a base, hydrolysis of the alkyl-(S,Z)-2,4,5-triamidopent-4-enoate to obtain a (S)-alkyl 2,5-diamido-4-oxopentanoate, acid catalyzed hydrolysis of the (S)-alkyl 2,5-diamido-4-oxopentanoate followed by reaction with a metal thiocyanate to obtain the thiohistidine, protection of the sulfur of thiohistidine as the tert-butyl thioether, dialkylation of the primary amine to obtain a tertiary amine, quaternization of the tertiary amine, and removal of the protecting group to obtain the desired (S)-3-(2-mercapto-1H-imidazol-5-yl)-2-(trialkylammonio)propanoate (I). This process affords a better yield and is capable of practical application at large scale.
- -
-
Page/Page column 6; 7
(2009/04/24)
-
- Histidine and deuterium labelled histidine by asymmetric catalytic reduction with gaseous H2 or D2; the role of strong non-coordinating acids
-
An efficient and convenient route for the preparation of natural and unnatural histidine by asymmetric hydrogenation with rhodium-phosphine complexes is described. The reductions were performed in the presence of HBF4 to generate an essential imidazolyl cation. Stereoselective incorporation of D2 in the α,β-positions was obtained by catalytic deuteration in the presence of MeOD.
- Cesarotti,Rimoldi,Zerla,Aldini
-
p. 273 - 278
(2008/09/19)
-
- Synthesis of metal-(pentadentate-salen) complexes: Asymmetric epoxidation with aqueous hydrogen peroxide and asymmetric cyclopropanation (salenH 2: N,N′-bis(salicylidene)ethylene-1,2-diamine)
-
It is known that the rates and stereochemical outcomes of epoxidations and cyclopropanations using a metallosalen (salenH2: N,N′- bis(salicylidene)ethylene-1,2-diamine) complex as catalyst are affected by a trans effect of the apical ligand of the complex. By taking into consideration this trans effect, we have synthesized optically active pentadentate salen ligands bearing an imidazole or pyridine derivative as the fifth coordinating group, and have prepared the corresponding manganese(III) and cobalt(II) complexes, in which the fifth ligand is expected to intramolecularly coordinate to the metal center and exert a trans effect. Indeed, high enantioselectivity has been achieved in epoxidations using aqueous hydrogen peroxide as the terminal oxidant and in cyclopropanations with these complexes as catalysts. In general, metallosalen-catalyzed reactions have been carried out in the presence of an excess of a donor ligand; however, the present reactions do not need the addition of any extra donor ligand.
- Shitama, Hiroaki,Katsuki, Tsutomu
-
p. 4849 - 4858
(2008/02/03)
-
- Brucella suis histidinol dehydrogenase: Synthesis and inhibition studies of a series of substituted benzylic ketones derived from histidine
-
Brucella spp. is the causative agent of brucellosis (Malta fever), which is the most widespread zoonosis worldwide. The pathogen is capable of establishing persistent infections in humans which are extremely difficult to eradicate even with antibiotic therapy. Moreover, Brucella is considered as a potential bioterrorism agent. Histidinol dehydrogenase (HDH, EC 1.1.1.23) has been shown to be essential for the intramacrophagic replication of this pathogen. It therefore constitutes an original and novel target for the development of anti-Brucella agents. In this work, we cloned and overexpressed the HDH-encoding gene from Brucella suis, purified the protein and evidenced its biological activity. We then investigated the inhibitory effects of a series of substituted benzylic ketones derived from histidine. Most of the compounds reported here inhibited B. suis HDH in the lower nanomolar range and constitute attractive candidates for the development of novel anti-Brucella agents.
- Abdo, Marie-Rose,Joseph, Pascale,Boigegrain, Rose-Anne,Liautard, Jean-Pierre,Montero, Jean-Louis,Koehler, Stephan,Winum, Jean-Yves
-
p. 4427 - 4433
(2008/03/13)
-
- Enantioselective ester hydrolysis catalyzed by imprinted polymers. 2
-
Highly cross-linked network polymers prepared by molecular imprinting catalyzed enantioselectively the hydrolysis of N-tert-butoxycarbonyl phenylalanine-p-nitrophenyl ester (BOCPheONP). The templates were designed to allow incorporation of the key catalytic elements, found in the proteolytic enzyme chymotrypsin, into the polymer active sites. Three model systems were evaluated. These were constructed from a chiral phosphonate analogue of phenylalanine (series A, C) or L-phenylalanine (series B) attached by a labile ester linkage to an imidazole-containing vinyl monomer. Free radical copolymerization of the template with methacrylic acid (MAA) and ethylene glycol dimethacrylate (EDMA) gave a highly cross-linked network polymer. The templates could be liberated from the polymers by hydrolysis, giving catalytically active sites envisaged to contain an enantioselective binding site, a site complementary to a transition state like structure (series A, C), and a hydroxyl, imidazole, and carboxylic acid group at hydrogen bond distance. As predicted, the enantiomer of BOCPheONP complementary to the configuration of the template was preferentially hydrolyzed with D-selectivity for the series A polymers (kD/kL= 1.9) and L-selectivity for the series B polymers (kL/kD = 1.2). The maximum rate enhancement, when compared with a control polymer, prepared using a benzoyl-substituted imidazole monomer as template, was 2.5, and comparing with the imidazole monomer in solution, a maximum rate enhancement of 10 was observed. The catalytic activity was higher for polymers subjected to the nucleophilic treatment. This was explained by a higher site density and flexibility of the polymer matrix caused by this treatment. In a comparison of template rebinding to polymers imprinted with a template containing either a carboxylate (planar ground state structure) or a phosphonate (tetrahedral transition state like structure) functionality, it was observed that imprinted polymers are able to discriminate between a transition state like and a ground state structure for transesterification. However the influence of transition state stabilization on the observed rate enhancements remains obscure. Only at acidic pH's was catalysis observed, whereas at basic pH's the polymers inhibit the reaction. At a later stage, the catalytic activity of the polymers for nonactivated D- and L-phenylalanine ethyl esters was investigated. A rate enhancement of up to 3 was observed when compared to the blank. Most important, however, the polymers imprinted with a D template preferentially hydrolyzed the D-ethyl ester and exhibited saturation kinetics.
- Sellergren,Karmalkar,Shea
-
p. 4009 - 4027
(2007/10/03)
-
- Synthesis and in vitro pharmacology of a series of new chiral histamine H3-receptor ligands: 2-(R and S)-amino-3-(1H-imidazol-4(5)-yl)propyl ether derivatives
-
To investigate stereospecificity and the mechanism of activation of the histamine H3-receptor, a series of 2-(R and S)-amino-3-(1H-imidazol-4(5)- yl)propyl ether derivatives were synthesized. In these compounds, the structures of the well-known antagonist iodoproxyfan and the full agonists R- or S-(α)-methylhistamine were combined in one molecule. The obtained 'hybrid' molecules were tested for H3-receptor affinity on rat cerebral cortex. Some selected compounds were further screened for H3-receptor functional activity with GTPγ[35S] autoradiography studies using rat brain tissue sections. The affinity of all the synthesized compounds (-log K(i) = 5.9-7.9) was lower than that found for iodoproxyfan or two of its analogues; however, the compounds showed stereospecificity. The S-configuration of the series of 2-amino-3-(1H-imidazol-4(5)-yl)propyl ether derivatives, which resembles the stereochemistry of R-(α)-methylhistamine, was more favorable. Incorporation of an amino group in the propyl chain of iodoproxyfan and analogues did not alter the antagonistic behavior for compounds with an aromatic side chain. However, when also the aromatic moiety was replaced by a cyclohexyl group, the compounds behaved as agonists. This indicates that an interaction between the side chain amino group and the H3-receptor protein is involved in H3-receptor activation. The 2-(S)-amino-3-(1H-imidazol-4(5)- yl)propyl cyclohexylmethyl ether (23) has H3-receptor agonistic properties with high affinity for the histamine H3-receptor (-log K(i) = 7.9 ± 0.2) and might serve as a useful tool for further studies concerning drug design and receptor-ligand interactions.
- Kovalainen, Jari T.,Christiaans, Johannes A. M.,Kotisaari, Sanna,Laitinen, Jarmo T.,M?nnist?, Pekka T.,Tuomisto, Leena,Gynther, Jukka
-
p. 1193 - 1202
(2007/10/03)
-
- Preparation of D-histidine and derivatives thereof from L-histidine
-
D-histidine and its derivatives are manufactured from L-histidine, by mixing L-histidine and tartaric acid with an aldehyde in acetic acid medium and thereafter precipitating D-histidine tartrate from the reaction mass. Pure D-histidine can then be recovered from the crude D-histidine tartrate.
- -
-
-
- N-HETEROCYCLIC ALCOHOL DERIVATIVES
-
Compounds of the formula STR1 wherein R 1 is an N-heterocyclic group as defined herein, are disclosed. These compounds are inhibitors of renin and therefore useful as cardiovascular agents.
- -
-
-
- Cyclic dipeptide enantiomers
-
The invention provides novel cyclic dipeptide enantiomers comprising (R)-histidine or a derivative thereof as one of the amino acid residues. These compounds are useful a catalysts for production of (S) -α--cyanomethyl alcohols from aldehydes.
- -
-
-
- Coordination Modes of Histidine. 3. Stereochemistry of Copper(II) Complexes Related to Pyridoxal Catalysis
-
Copper(II) complexes of Shiff bases derived from pyridoxal, salicylaldehyde, or pyruvic acid and histidine, histidine methyl ester, and representative amino acids with nonpolar side chains have been prepared by metal ion template synthesis.The mode of coordination to copper(II) of the histidine residues in these complexes have been investigated by circular dichroism spectroscopy.The complexes derived from amino acids with nonpolar side chains provide appropriate references for the glycine-like coordination mode, while the derivatives of histidine methyl ester are appropriate references for the histamine-like mode.The histidine residues exhibit a striking tendency to bind copper(II) through chelate ring types complementary to those of the fused carbonyl residue.Thus, in the complexes derived from pyridoxal and salicylaldehyde the histidine residues bind glycine-like, whereas in those derived from pyruvic acid the histidine residues bind histamine-like.The conformation of the coordinated Shiff-base ligands has been deduced from the circular dichroism spectra of the complexes and discussed in relation to vitamin B6 model reactions.The ESR spectra of these complexes were also investigated in different solvents to establish the donor sets and the ligand field simmetry in solution.The spectra show the pattern typical for tetragonal symmetry (g** > g*), and the magnetic parameters were used to compute the molecular orbital coefficients that describe the bonding character in the complexes.The electronic excitation energies required in the calculations were deduced from the circular dichroism spectra.
- Casella, Luigi,Gillotti, Michele,Pacchioni, Gianfranco
-
p. 2386 - 2396
(2007/10/02)
-
