Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
Add more filters










Publication year range
1.
Nat Prod Res ; 37(21): 3572-3579, 2023.
Article in English | MEDLINE | ID: mdl-35762388

ABSTRACT

Three new triterpenoid glycosides, 2α,3α,23,24-tetrahydroxyurs-12,19- dien-oic acid 28-O-ß- D -glucopyranoside (1), 2α,3ß,23,24-tetrahydroxyurs-12, 19(29) -dien-28-oic acid 28-O-ß- D -glucopyranoside (2), and 2α,3ß,23,24-tetrahydroxyurs-12, 18-dien-28-oic acid 28-O-ß- D -glucopyranoside (3) were isolated from Aronia melanocarpa (Michx.) Elliott. Their structures were elucidated by extensive spectroscopic methods. All the isolated compounds displayed moderate inhibitory activity against nitric oxide production in macrophages.

2.
Chem Commun (Camb) ; 51(47): 9662-5, 2015 Jun 14.
Article in English | MEDLINE | ID: mdl-25977950

ABSTRACT

We developed a new strategy for the functionalization of hyaluronic acid by chemical modification of its C-6 hydroxyl groups through an ether bond to obtain a cysteine-hyaluronic acid conjugate. This conjugate is suitable to prepare injectable and in situ formed hydrogels cross-linked by native chemical ligation and Michael addition under mild conditions.


Subject(s)
Biocompatible Materials/chemistry , Cross-Linking Reagents/chemistry , Cysteine/chemistry , Hyaluronic Acid/chemistry , Hydrogels/chemistry
3.
Colloids Surf B Biointerfaces ; 85(1): 48-55, 2011 Jun 15.
Article in English | MEDLINE | ID: mdl-21109407

ABSTRACT

Three random copolymers poly(2-methacryloyloxyethyl phosphorylcholine-co-methacrylic acid) (PMAs) were synthesized by free radical polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylic acid (MA) with different monomer ratios under monomer-starved conditions. The synthesized PMA polyanions were assembled on chitosan (CS) film surfaces via electrostatic interactions. Using layer by layer (LbL) assembly with PMA polyanion and chitosan polycation, PMA/CS multilayer thin films with phosphorylcholine groups on the outer surfaces were fabricated. The modified surfaces were characterized by dynamic contact angle (DCA), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Hemocompatibility of the surfaces was estimated by protein adsorption and platelet adhesion measurements. The results indicated that cell outer membrane mimetic structures were formed on the modified surfaces with PMA as the outermost layer, and the hemocompatibility of the modified surfaces was significantly improved. This facile method of fabricating cell outer membrane mimetic surfaces may have potential applications in the fields of hemocompatible coatings, drug delivery, and tissue engineering.


Subject(s)
Biocompatible Materials/chemistry , Chitosan/chemistry , Phosphorylcholine/chemistry , Polymers/chemistry , Biocompatible Materials/adverse effects , Cell Membrane/drug effects , Platelet Aggregation/drug effects , Polyelectrolytes
4.
Tetrahedron Lett ; 51(18): 2403-2405, 2010 May 01.
Article in English | MEDLINE | ID: mdl-20543896

ABSTRACT

Direct acetonide protection of the catechol of dopamine has proven to be problematic due to formation of Pictet-Spengler isoquinolines. Here we report an efficient method for acetonide protection of dopamine, allowing preparation of a dopamine prodrug without complications from the Pictet-Spengler reaction. Acetonide-protected dopamine was first synthesized by pre-protecting the amino group with phthaloyl followed by refluxing with 2,2-dimethoxypropane in the presence of TsOH. Further work demonstrated that Fmoc or trifluoroacetyl were also suitable N-protective groups, while Boc-protected dopamine gave an isoquinoline product. Acetonide-protected dopamine was coupled to DHA (all cis-4,7,10,13,16,19-docosahexaenoic acid) to produce the N-DHA-dopamine prodrug in high purity.

5.
Biomaterials ; 31(2): 308-14, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19782393

ABSTRACT

Pancreatic islet encapsulation within semi-permeable materials has been proposed for transplantation therapy of type I diabetes mellitus. Polymer hydrogel networks used for this purpose have been shown to provide protection from islet destruction by immunoreactive cells and antibodies. However, one of the fundamental deficiencies with current encapsulation methods is that the permselective barriers cannot protect islets from cytotoxic molecules of low molecular weight that are diffusible into the capsule material, which subsequently results in beta-cell destruction. Use of materials that can locally inhibit the interaction between the permeable small cytotoxic factors and islet cells may prolong the viability and function of encapsulated islet grafts. Here we report the design of anti-inflammatory hydrogels supporting islet cell survival in the presence of diffusible pro-inflammatory cytokines. We demonstrated that a poly(ethylene glycol)-containing hydrogel network, formed by native chemical ligation and presenting an inhibitory peptide for islet cell surface IL-1 receptor, was able to maintain the viability of encapsulated islet cells in the presence of a combination of cytokines including IL-1 beta, TNF-alpha, and INF-gamma. In stark contrast, cells encapsulated in unmodified hydrogels were mostly destroyed by cytokines which diffused into the capsules. At the same time, these peptide-modified hydrogels were able to efficiently protect encapsulated cells against beta-cell specific T-lymphocytes and maintain glucose-stimulated insulin release by islet cells. With further development, the approach of encapsulating cells and tissues within hydrogels presenting anti-inflammatory agents may represent a new strategy to improve cell and tissue graft function in transplantation and tissue engineering applications.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cell Culture Techniques/methods , Hydrogels/pharmacology , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Peptides/pharmacology , Animals , Cell Death/drug effects , Cell Line, Tumor , Cell Separation , Cell Survival/drug effects , Cross-Linking Reagents/pharmacology , Cytokines/metabolism , Cytoprotection/drug effects , Glucose/pharmacology , Hydrogels/chemistry , Inflammation Mediators/metabolism , Insulin/metabolism , Insulin Secretion , Insulin-Secreting Cells/immunology , Insulin-Secreting Cells/metabolism , Mice , Peptides/chemistry , T-Lymphocytes, Cytotoxic/cytology , T-Lymphocytes, Cytotoxic/drug effects
6.
Biomacromolecules ; 10(8): 2194-200, 2009 Aug 10.
Article in English | MEDLINE | ID: mdl-19601644

ABSTRACT

We describe the use of native chemical ligation (NCL) reaction to covalently cross-link soluble polymers into hydrogels. Macromonomers consisting of a four-armed poly(ethylene glycol) (PEG) core end-functionalized with either thioester or N-terminal cysteine peptide were designed and synthesized. Upon mixing aqueous solutions of the thioester and N-terminal cysteine macromonomers, rigid hydrogels formed within minutes. The gelation time was affected by choice of buffer, pH, polymer concentration, reaction temperature, and chemical composition of the N-terminal cysteine conjugate. The kinetics of gel formation and the viscoelastic behavior of selected hydrogels were further studied by oscillatory rheology, which demonstrated a minimum gel formation time of approximately two minutes and the formation of an elastic cross-linked hydrogel via the NCL reaction. A useful feature of this hydrogel strategy is the regeneration of thiol functional groups as a result of the NCL reaction, thereby allowing functionalization of the polymer hydrogel with biomolecules. This was demonstrated by conjugation of a maleimide-GRGDSPG-NH(2) peptide to an NCL hydrogel, permitting the attachment of human mesenchymal stem cells (hMSCs) on the hydrogel. Due to the mild reaction conditions, chemoselectivity, and potential for biological functionalization, our approach may prove useful as a general method for hydrogel formation, including hydrogels intended for biomedical applications.


Subject(s)
Biocompatible Materials/chemistry , Hydrogels/chemistry , Maleimides/chemistry , Mesenchymal Stem Cells/metabolism , Peptide Fragments/chemistry , Polyethylene Glycols/chemistry , Biocompatible Materials/metabolism , Cross-Linking Reagents , Humans , Hydrogels/metabolism , Maleimides/metabolism , Peptide Fragments/metabolism , Polyethylene Glycols/metabolism
7.
Tetrahedron Lett ; 49(38): 5519-5521, 2008 Sep 15.
Article in English | MEDLINE | ID: mdl-19759805

ABSTRACT

We report a facile approach to the synthesis of acetonide and Fmoc protected 3,4-dihydroxyphenylalanine (DOPA), Fmoc-DOPA(acetonide)-OH. By protecting the amino group of DOPA with a phthaloyl group and the carboxyl group as a methyl ester, acetonide protection of the catechol of DOPA derivative was realized in the presence of p-toluenesulfonic acid. Following removal of protecting groups, the intermediate was converted to Fmoc-DOPA(acetonide)-OH, which was successfully incorporated into a short DOPA-containing peptide, derived from marine tubeworm cement proteins Pc1 and Pc2.

8.
Anal Chem ; 79(19): 7275-85, 2007 Oct 01.
Article in English | MEDLINE | ID: mdl-17713965

ABSTRACT

We describe a new method for encoded synthesis, efficient on-resin screening, and rapid unambiguous sequencing of combinatorial peptide libraries. An improved binary tag system for encoding peptide libraries during synthesis was designed to facilitate unequivocal assignment of isobaric residues by MALDI-TOF MS analysis. The improved method for encoded library synthesis was combined with a new versatile on-resin screening strategy that permitted multiple stages and types of screening to be employed successively on one library under mild conditions. The new method facilitated a combinatorial study of transglutaminase (TGase) enzyme substrate peptides, revealing new details of the effect of amino acid composition on TGase substrates. The approach was first demonstrated for an encoded library (130,321 compounds) of lysine pentapeptide substrates of TGase, synthesized using the "split-mix" method. The library was reacted on-resin with TGase enzyme and a soluble desthiobiotin labeled glutamine substrate. Initial screening was performed by adsorbing streptavidin-coated magnetic microparticles onto library beads, followed by magnetic separation. The differential binding affinities of desthiobiotin and biotin for streptavidin were exploited to release the magnetic microparticles and regenerate the desthiobiotin-labeled resin beads for further screening by flow-cytometry-based automated bead sorting, resulting in 345 beads that were sequenced by MALDI-TOF MS analysis. A second library consisted of encoded glutamine hexapeptide substrates, which was reacted on-resin with TGase enzyme and a soluble desthiobiotin-labeled cadaverine. Two-stage screening identified 267 glutamine peptides as TGase-reactive, of which 21 were further analyzed by solution-phase enzyme kinetics. Kinetic results indicated that the peptide PQQQYV from the library has a 68-fold greater substrate specificity than the best known glutamine substrate QQIV. The new encoding and screening strategies described here are expected to be broadly applicable to synthesis and screening of combinatorial peptide libraries in the future.


Subject(s)
Combinatorial Chemistry Techniques , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Magnetics
9.
J Am Chem Soc ; 126(46): 15223-30, 2004 Nov 24.
Article in English | MEDLINE | ID: mdl-15548019

ABSTRACT

The ability to present cell adhesion molecule (CAM) ligands in controlled amounts on a culture surface would greatly facilitate the control of cell growth and differentiation. Supported lipid monolayer/bilayer systems have previously been developed that allow for presentation of CAM ligands for cell interaction; however, these systems have employed peptide loadings much higher than those used in poly(ethylene glycol) (PEG)-based immobilization systems. We report the development of synthetic methods that can be used for the efficient and versatile creation of many linear and cyclic lipid-linked peptide moieties. Using RGD-based peptides for the alpha5beta1 integrin as a model system, we have demonstrated that these lipopeptides support efficient cell binding and spreading at CAM ligand loadings as low as 0.1 mol %, which is well below that previously reported for supported lipid systems. Engineered lipopeptide-based surfaces offer unique presentation options not possible with other immobilization systems, and the high activity at low loadings we have shown here may be extremely useful in presenting multiple CAM ligands for studying cell growth, differentiation, and signaling.


Subject(s)
Lipoproteins/chemistry , Lipoproteins/metabolism , Oligopeptides/chemistry , Oligopeptides/metabolism , Phospholipids/chemistry , Phospholipids/metabolism , Cell Adhesion , Cell Adhesion Molecules/chemistry , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , Endothelium, Vascular/cytology , Hematopoietic Stem Cells/cytology , Humans , Integrin alpha5beta1/chemistry , Integrin alpha5beta1/metabolism , Ligands , Lipopeptides , Lipoproteins/chemical synthesis , Oligopeptides/chemical synthesis , Peptides, Cyclic/chemical synthesis , Peptides, Cyclic/chemistry , Peptides, Cyclic/metabolism , Substrate Specificity , Surface Properties
10.
J Am Chem Soc ; 125(47): 14298-9, 2003 Nov 26.
Article in English | MEDLINE | ID: mdl-14624577

ABSTRACT

Short peptide substrates with high specificity toward transglutaminase (TGase) enzyme were designed, characterized, and coupled to a biocompatible polymer, allowing for rapid enzymatic cross-linking of peptide-polymer conjugates into hydrogels. Eight acyl acceptor Lys-peptide substrates and three acyl donor Gln-peptide substrates were rationally designed and synthesized. The kinetic constants of these peptides toward tissue transglutaminase were measured by enzyme assay using RP-HPLC analysis with the aid of LC-ESI/MS. Several acyl donor and acyl acceptor peptides with high specificities toward TGase were identified, including a few containing the unusual amino acid l-3,4-dihydroxylphenylalanine (DOPA), which is found in the adhesive proteins secreted by marine and freshwater mussels. Acyl donor and acyl acceptor peptides with high substrate specificities were separately coupled to branched poly(ethylene glycol) (PEG) polymer molecules. Equimolar solutions of these polymer-peptide conjugates rapidly formed hydrogels in less than 2 min in the presence of transglutaminase under physiological conditions. The use of biocompatible building blocks, their rapid solidification from a liquid precursor under physiologic conditions, and the ability to incorporate adhesive amino acid residues using biologically benign enzymatic cross-linking are advantageous properties for the use of such materials for tissue repair, drug delivery, and tissue engineering applications.


Subject(s)
Biocompatible Materials/chemical synthesis , Hydrogels/chemical synthesis , Oligopeptides/chemistry , Transglutaminases/metabolism , Biocompatible Materials/chemistry , Dihydroxyphenylalanine/chemistry , Dihydroxyphenylalanine/metabolism , Hydrogels/metabolism , Oligopeptides/chemical synthesis , Oligopeptides/metabolism , Polyethylene Glycols/chemistry , Substrate Specificity , Transglutaminases/chemistry
11.
J Am Chem Soc ; 125(14): 4253-8, 2003 Apr 09.
Article in English | MEDLINE | ID: mdl-12670247

ABSTRACT

A new biomimetic strategy for modification of biomaterial surfaces with poly(ethylene glycol) (PEG) was developed. The strategy exploits the adhesive characteristics of 3,4-dihydroxyphenylalanine (DOPA), an important component of mussel adhesive proteins, to anchor PEG onto surfaces, rendering the surfaces resistant to cell attachment. Linear monomethoxy-terminated PEGs were conjugated either to a single DOPA residue (mPEG-DOPA) or to the N-terminus of Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys (mPEG-MAPD), a decapeptide analogue of a protein found in Mytilus edulis adhesive plaques. Gold and titanium surfaces were modified by adsorption of mPEG-DOPA and mPEG-MAPD from solution, after which surface analysis by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectroscopy confirmed the presence of immobilized PEG on the surface. The ability of modified surfaces to resist cell attachment was examined by culturing 3T3 fibroblasts on the surfaces for up to 14 days. Quantitative image analysis revealed that cell adhesion to mPEG-DOPA and mPEG-MAPD modified surfaces decreased by as much as 98% compared to control surfaces. Modified Ti surfaces exhibited low cell adhesion for up to 2 weeks in culture, indicating that the nonfouling properties of mPEG-DOPA and mPEG-MAPD treated surfaces persist for extended periods of time. This strategy paradoxically exploits the strong fouling characteristics of MAP analogues for antifouling purposes and may be broadly applied to medical implants and diagnostics, as well as numerous nonmedical applications in which the minimization of surface fouling is desired.


Subject(s)
Biomimetic Materials/chemistry , Coated Materials, Biocompatible/chemistry , Dihydroxyphenylalanine/chemistry , Polyethylene Glycols/chemistry , Proteins/chemistry , 3T3 Cells , Animals , Bivalvia/chemistry , Cell Adhesion , Mice , Oligopeptides/chemistry , Spectrometry, Mass, Secondary Ion , Surface Properties
SELECTION OF CITATIONS
SEARCH DETAIL
...