- The effect of l-DOPA hydroxyl groups on the formation of supramolecular hydrogels
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Fmoc-l-DOPA-d-Oxd-OH was prepared starting from commercially available l-DOPA. Its gelation ability was tested by comparison with Fmoc-l-Tyr-d-Oxd-OH and Fmoc-l-Phe-d-Oxd-OH using ten different triggers. Among them, only GdL, CaCl2 and ZnCl2 form strong hydrogels with the three gelators. The analysis of the aerogels obtained by freeze drying the hydrogels show that the three gelators always induce the formation of dense networks, which strongly depend on the nature of the gelator. Rheological analysis of these samples demonstrates that stronger gels were obtained using the l-Tyr containing gelator, while the l-DOPA containing hydrogels were characterized by a storage modulus approximately one order of magnitude lower. Finally, the l-Phe containing gelators show a different trend with respect to the other samples depending on the trigger used. All the hydrogels show a thixotropic behaviour at the molecular level. These results indicate that hydrogel formation is sensitive to both the number of the hydroxyl moieties on the aromatic rings and trigger used.
- Zanna, Nicola,Iaculli, Debora,Tomasini, Claudia
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Read Online
- COMPOSITIONS AND METHODS FOR THE TREATMENT OF PAIN AND DEPENDANCE DISORDERS
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Provided herein are (e.g., controlled release) compositions for the treatment of acute or chronic diseases or disorders. Described herein are processable opioid conjugates. Also described herein are compositions and methods for the treatment of central nervous system (CNS) diseases or disorders including chronic pain (e.g., cancer pain), acute pain, opioid addiction, alcohol addiction, alcohol dependence, opioid-induced constipation, and narcotic depression. Said compositions and methods comprise opioid agonists and/or opioid antagonists, which demonstrate CNS activity and/or other desirable activities. Injection of said compositions subcutaneously or intraspinally provides therapeutic benefit to individuals suffering from CNS diseases or disorders
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- Genetically Engineered Polypeptide Adhesive Coacervates for Surgical Applications
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Adhesive hydrogels have been developed for wound healing applications. However, their adhesive performance is impaired dramatically due to their high swelling on wet tissues. To tackle this challenge, we fabricated a new type of non-swelling protein adhesive for underwater and in vivo applications. In this soft material, the electrostatic complexation between supercharged polypeptides with oppositely charged surfactants containing 3,4-dihydroxylphenylalanine or azobenzene moieties plays an important role for the formation of ultra-strong adhesive coacervates. Remarkably, the adhesion capability is superior to commercial cyanoacrylate when tested in ambient conditions. Moreover, the adhesion is stronger than other reported protein-based adhesives in underwater environment. The ex vivo and in vivo experiments demonstrate the persistent adhesive performance and outstanding behaviors for wound sealing and healing.
- Herrmann, Andreas,Li, Bo,Li, Jingjing,Liu, Kai,Ma, Chao,Sun, Jing,Wang, Zili,Xiao, Lingling,Zhang, Hongjie,Zhao, Kelu,Zhou, Yu
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p. 23687 - 23694
(2021/10/08)
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- Water-soluble L-DOPA esters
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The present invention relates to novel compounds of the formula I, methods for their preparation and their use for treatment of diseases. The invention discloses the synthesis of levodopa (L-DOPA) esters by coupling polyhydroxy compounds or their derivatives to the L-DOPA carboxyl group. The synthesis allows to produce L-DOPA derivatives which are highly soluble in water as well as aqueous and biocompatible liquids and have an improved hydrolytic stability in water or aqueous and biocompatible media for an application over several days. The invention helps producing L-DOPA substances for applications in the fields of medicine, biology and medical engineering as well as in the pharmaceutical industry.
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- Large Amino Acid Transporter 1 Selective Liposomes of l -DOPA Functionalized Amphiphile for Combating Glioblastoma
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Despite significant progress in neurosurgery and radiation therapy during the past decade, overall survivability (OS) of glioblastoma patients continues to be less than 2 years. The scope of systemic chemotherapy is greatly limited by poor drug transport
- Bhunia, Sukanya,Vangala, Venugopal,Bhattacharya, Dwaipayan,Ravuri, Halley Gora,Kuncha, Madhusudana,Chakravarty, Sumana,Sistla, Ramakrishna,Chaudhuri, Arabinda
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p. 3834 - 3847
(2017/11/15)
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- Similar EDTA ligand containing O-phenolic hydroxyl, as well as non-gadolinium magnetic resonance contrast agent and preparation method thereof
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The invention discloses a similar EDTA ligand namely 2,2',2'',2'''-((3-(3,4-dihydroxyphenyl) propane-1,2diyl) ethylene diamine tetraacetic containing O-phenolic hydroxyl, a non-gadolinium paramagnetic metal coordination compound namely a magnetic resonanc
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- MULTIMODAL CONTRAST AND RADIOPHARMACEUTICAL AGENT FOR AN IMAGING AND A TARGETED THERAPY GUIDED BY IMAGING
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The present invention relates to a multimodal contrast and radiopharmaceutical agent for an imaging and a targeted therapy guided by imaging.
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Page/Page column 37
(2013/06/05)
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- Design, synthesis, and preliminary pharmacological evaluation of new imidazolinones as l-DOPA prodrugs
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l-DOPA, the immediate biological precursor of dopamine, is still considered the drug of choice in the treatment of Parkinson's disease. However, therapy with l-DOPA is associated with a number of acute problems. With the aim to increase the bioavailability after oral administration, we designed a multi-protected l-DOPA prodrugs able to release the drug by both spontaneous chemical or enzyme catalyzed hydrolysis. The new compounds have been synthesized and preliminarily evaluated for their water solubility, log P, chemical stability, and enzymatic stability. The results indicate that the incorporation of the amino acidic moiety of l-DOPA into an imidazoline-4-one ring provides prodrugs sufficiently stable to potentially cross unchanged the acidic environment of the stomach, and to be absorbed from the intestine. They also might be able to release l-DOPA in human plasma after enzymatic hydrolysis. The ability of prodrugs 6a-b to increase basal levels of striatal DA, and influence brain neurochemistry associated with dopaminergic activity following oral administration, as well as the radical-scavenging activity against DPPH for compounds 6a-b and 15a are also reported.
- Giorgioni, Gianfabio,Claudi, Francesco,Ruggieri, Sabrina,Ricciutelli, Massimo,Palmieri, Giovanni F.,Stefano, Antonio Di,Sozio, Piera,Cerasa, Laura S.,Chiavaroli, Annalisa,Ferrante, Claudio,Orlando, Giustino,Glennon, Richard A.
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experimental part
p. 1834 - 1843
(2010/05/02)
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- Design, synthesis and biological evaluation of l-dopa amide derivatives as potential prodrugs for the treatment of Parkinson's disease
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A range of amide derivatives of l-dopa were synthesized and investigated for their pharmacological activity and their ability to be converted to l-dopa using the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat, as an experimental model of Parkinson's
- Zhou, Tao,Hider, Robert C.,Jenner, Peter,Campbell, Bruce,Hobbs, Christopher J.,Rose, Sarah,Jairaj, Mark,Tayarani-Binazir, Kayhan A.,Syme, Alexander
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experimental part
p. 4035 - 4042
(2010/10/02)
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- METHOD OF PREPARING DENDRITIC DRUGS
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Synthetic design of drug-incorporated novel dendrimer structures for quantitatively controlled drug delivery. The dendritic drugs have better control and thus a quantitative drug release can be obtained. There are no prior art dendritic drugs that control release both sequentially and quantitatively like the dendritic drugs disclosed herein. The dendritic drugs are formed by incorporating multiple same type drug units or more than two different drug types into a dendritic cascade structure to form a dendrimer drug.
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Page/Page column 20-21; 23; 28; sheet 17
(2010/11/28)
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- AMINO ACID DERIVATIVES
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Compounds of formula (I) are active as dopaminergic compounds or as compounds which or as compounds which diminish the symptoms of dopamine deficiency.: wherein: R1 and R2 are independently selected from -C(=O)R5 or -C(=O)OR5; or one of R1 and R2 is hydrogen and the other is -C(=O)R5 or -C(=O)OR5; R3 and R4 are independently selected from hydrogen, optionally substituted C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, or C2-C6 alkynyl, -CH2Q, -C(=O)R5, -C(=O)OR5, - C(=O)NR5R6, or R5 is hydrogen or optionally substituted C1-C6 alkyl or -CH2Q; R6 is hydrogen or optionally substituted C1-C6 alkyl Or -CH2Q; and Q is an optionally substituted monocyclic carbocyclic or heterocyclyl ring of 3 to 6 ring atoms.
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Page/Page column 13-14
(2008/06/13)
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- Synthesis and characterization of water-soluble and photostable L-DOPA dendrimers
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A small drug molecule, L-DOPA, was converted into well-defined dendritic macromolecules. Their monodisperse nature was shown by NMR, MALDI-TOF-MS, and PAGE. A third-generation L-Dopa dendrimer contained 30 L-Dopa residues, which made up its core, branches, and periphery. Individual L-Dopa moieties in the dendrimer were connected to one another via hydrolyzable diester linkages. These Dopa dendrimers showed a 20-fold increase in aqueous solubility and enhanced photostability in solutions over L-Dopa under identical conditions.
- Tang, Shengzhuang,Martinez, Lynda J.,Sharma, Ajit,Chai, Minghui
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p. 4421 - 4424
(2007/10/03)
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- Synthesis of terminally protected (S)-β3-H-DOPA by Arndt-Eistert homologation: An approach to crowned β-peptides
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Terminally protected Boc-(S)-β3-H-DOPA-OMe has been synthesized from l-DOPA by the Arndt-Eistert homologation procedure. During the synthesis, the side-chain catechol group was temporarily protected by benzylation. The absence of racemization w
- Gaucher, Anne,Dutot, Laurence,Barbeau, Olivier,Hamchaoui, Wahib,Wakselman, Michel,Mazaleyrat, Jean-Paul
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p. 857 - 864
(2007/10/03)
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- Synthesis of [18-C-6]-β3-(L)-DOPA, first β-amino acid with a crown-ether receptor side-chain
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Terminally protected Boc-β3-(L)-DOPA-OMe has been synthesized from (L)-DOPA by the Arndt-Eistert homologation procedure. Then, a first crown-ether derivative, Boc-[18-C-6]-β3-(L)-DOPA-OMe, has been obtained by bis-O-alkylation of the
- Gaucher, Anne,Barbeau, Olivier,Hamchaoui, Wahib,Vandromme, Lucie,Wright, Karen,Wakselman, Michel,Mazaleyrat, Jean-Paul
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p. 8241 - 8244
(2007/10/03)
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- Synthesis of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine as potential prodrug of L-dopa
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The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P=2.153 ± 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it is turned into L-Dopa. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Cingolani, Gian Mario,Di Stefano, Antonio,Mosciatti, Barbara,Napolitani, Fabrizio,Giorgioni, Gianfabio,Ricciutelli, Massimo,Claudi, Francesco
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p. 1385 - 1388
(2007/10/03)
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- pGlu-L-Dopa-Pro: A tripeptide prodrug targeting the intestinal peptide transporter for absorption and tissue enzymes for conversion
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Purpose. The purpose of this study is to investigate the characteristics of pGlu-L-Dopa-Pro as a prodrug of L-Dopa. Methods. pGlu-L-Dopa-Pro and L-Dopa-Pro were synthesized using the standard procedures of peptide synthesis. The conversion of pGlu-L-Dopa-Pro to L-Dopa was studied using pyroglutamyl aminopeptidase I and prolidase. With rats as the animal model, the stability of pGlu-L-Dopa-Pro in intestinal homogenates was determined, then the transport characteristics of pGlu-L-Dopa-Pro were studied using in-situ perfusion and Ussing chambers. Results. pGlu-L-Dopa-Pro, relatively stable in intestinal homogenates and intestinal fluid, had a dimensionless permeability of 1.8 at 0.04 mM. Its intestinal permeability was significantly inhibited by 20 mM captopril, by a mixture of dipeptides, 80 mM Gly-Gly and 5 mM Gly-Pro, and by 2 mM cephradine. Further, in Ussing chambers, its mucosal to serosal permeability decreased dramatically with concentration. Conversion studies showed that pGlu-L-Dopa-Pro was degraded by pyroglutamyl aminopeptidase I, an enzyme releasing the N-terminal pyroglutamic acid, with Vmax and Km of 0.6 μmole/min/g protein and 21 mM, respectively, and that L-Dopa-Pro was degraded by prolidase with Vmax and Km of 44 μmole/min/g protein and 0.48 mM, respectively. Conclusions. This tripeptide, a potential prodrug of L-Dopa, is absorbed by the intestinal peptide transporter, is relatively stable in the gut wall, and is converted to L-Dopa by peptidases with the cleavage by pyroglutamyl aminopeptidase I to L-Dopa-Pro as the rate limiting step.
- Bai
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p. 1101 - 1104
(2007/10/03)
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- Synthesis and α2-adrenoceptor effects of substituted catecholimidazoline and catecholimidazole analogues in human platelets
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It is known that the steric requirements for the interactions of catecholamines and catecholimidazolines with α1- and α2-adrenoceptors are different. New analogues of desoxycatecholimidazoline (1), desoxycatecholimidazole (3), benzylic hydroxyl substituted imidazole (4), and the aromatic fluorine substitution analogues of 1 at the 2 (5), 5 (6), and 6 (7) positions, and a set of asymmetric 4-substituted catecholimidazolines, S-8 and R-8, were prepared and tested for interaction with α2-adrenoceptors in human platelets. With the exception of 3, all compounds were selective for α-adrenoceptor-mediated responses in human platelets. Introduction of a double bond in imidazoline 1 to give an imidazole 3 or the introduction of a benzylic hydroxyl group to 3, as in 4, reduced the inhibition of platelet aggregation with a rank order potency of 1 > 3 > 4. Fluorine atom substitution at the 2-, 5-, or 6-positions only slightly modified the inhibitory activity of 1. Each analogue (1, 3-7) produced α2-mediated inhibition of platelet adenylate cyclase and can be classified as a partial agonist. The inhibition potency of S-8 and R-8 against epinephrine-induced aggregatory responses were greatly different, and only R-8 and 4 were α2-agonists on human platelet function. Our studies provide further evidence for the differential interaction of catecholamines and catecholimidazolines in α1- and α2-adrenoceptor systems.
- Miller,Hamada,Clark,Adejare,Patil,Shams,Romstedt,Kim,Intrasuksri,McKenzie,Feller
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p. 1138 - 1144
(2007/10/02)
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- Synthesis and Adhesive Studies of Marine Polypeptides
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The marine adhesive polydecapeptide (Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Dopa-Lys)n (n ca. 10) has been synthesized by coupling reactions, followed by polycondensation.The O-benzyl, O,O'-dibenzyl, and N-ε-2-chlorobenzyloxycarbonyl groups were used to protect
- Yamamoto, Hiroyuki
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p. 613 - 618
(2007/10/02)
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