Organocatalytic approach to amphiphilic comb-block copolymers capable of stereocomplexation and self-assembly

Biocompatible amphiphilic block copolymers comprised of poly(ethylene glycol) (PEG) as the hydrophilic component and a poly(methylcarboxytrimethylene carbonate) (PMTC) as a hydrophobic backbone having either poly(L-lactide) (L-PLA) or poly(D-lactide) (D-PLA) branches were prepared by organocatalytic ring-opening polymerization (ROP). The polycarbonate backbone was prepared by copolymerization of two different MTC-type monomers (MTCs) including a tetrahydropyranyloxy protected hydroxyl group, a masked initiator for a subsequent ROP step. Interestingly, the organic catalyst used in the ROP of MTCs was also effective for acetylation of the hydroxyl end-groups by the addition of acetic anhydride added after polymerization. Acidic deprotection of the tetrahydropyranyloxy (THP) protecting group on the carbonate chain generated hydroxyl functional groups that served as initiators for the ROP of either D- or L-lactide. Comb-shaped block copolymers of predictable molecular weights and narrow polydispersities (approximately 1.3) were prepared with up to 8-PLA branches. Mixtures of the D- and L-lactide based copolymers were studied to understand the effect of noncovalent interactions or stereocomplexation on the properties.     

Block copolymerization of α-amino acid N-carboxyanhydride initiated by vinyl polymers having a terminal amino group and the characterization of the block copolymers

Poly(methyl methacrylate) and polystyrene having terminal amino groups were synthesized by the radical polymerization of those monomers in the presence of 2-mercaptoethylammonium chloride as a chain-transfer agent. By the terminal group analysis and the molecular weight determination of the polymers, 0.5–1.3 amino groups were found in a chain of poly(methyl methacrylate) and 0.5–2.5 amino groups in a chain of polystyrene. Using these polymers having a terminal amino group as an initiator, the block polymerization of α-amino acid N-carboxyanhydride (NCA) was carried out. In the polymerizations of Glu(OBzl) NCA and Lys(Z) NCA by the poly(methyl methacrylate) initiator, the terminal amino group underwent a nucleophilic addition reaction to NCA and initiated the polymerization, yielding A-B-type block copolymers in a high yield. The same was observed in the polymerizations of Gly(OBzl) NCA and Lys(Z) NCA by the polystyrene initiator. By eliminating the protecting groups of the side chains of the polypeptide segment, the block copolymers poly(methyl methacrylate)-poly(Glu), poly(methyl methacrylate)-poly(Lys), polystyrene-poly(Glu) and polystyrene-poly(Lys) were synthesized with little side reactions. The side chain amino groups of poly(Lys) segment in the poly(methyl methacrylate)-poly(Lys) block copolymers were sulphonated or stearoylated successfully.     

Report on the use of poly(organophosphazenes) for the design of stimuli-responsive vesicles

A novel family of amphiphilic temperature- and pH-sensitive poly(organophosphazenes) with varying ratios of ethylene oxide, alkyl chains and free acid units was synthesized by living cationic polymerization. Depending on their composition, these poly(organophosphazenes) exhibited lower critical solution temperatures ranging from 32 to 44 degrees C, which were pH-dependent for copolymers bearing carboxylic acid groups. The alkylated copolymers were then anchored into phospholipid bilayers to obtain stimuli-responsive liposomes that released their content upon a change in temperature or pH. Such polymer/vesicle complexes could find practical applications for site-specific and intracellular drug delivery.     

Amphiphilic poly(L-lactide)-b-dendritic poly(L-lysine)s synthesized with a metal-free catalyst and new dendron initiators: chemical preparation and characterization

This study presents investigations on new approaches to novel biodegradable amphiphilic poly(L-lactide)-b-dendritic poly(L-lysine)s bearing well-defined structures. First, two new Boc-protected poly(L-lysine) dendron initiators G(2)OH 4 (generation = 2) and G(3)OH 6 (generation = 3) with hydroxyl end functional groups were efficiently derived from corresponding precursors 3 and 5 via methyl ester substitution with ethanolamine. Subsequently, two series of new diblock copolymers of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s (S1-S2, S3-S4) were prepared in chloroform through ring-opening copolymerization of poly(L-lactide)s with a metal-free catalyst of organic 4-(dimethylamino) pyridine (DMAP) in the presence of a corresponding new poly(L-lysine) dendron initiator. Further, molecular structures of the prepared new dendron initiators as well as those of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s bearing different dendron blocks and PLLA lengths were examined by means of nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), mass spectrometry (ESI-MS, MALDI-FTMS), and thermal gravimetric analysis (TGA). The results demonstrated successful formation of the synthetic precursors, functional dendron initiators, and new diblock copolymers. In addition, the very narrow molecular weight distributions (PDI = 1.10-1.14) of these poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s further indicated their well-defined molecular structures. After the efficient Boc-deprotection for the dendron amino groups with TFA/CH(2)Cl(2), new diblock poly(L-lactide)-b-dendritic poly(L-lysine)s bearing lipophilic PLLA and hydrophilic dendritic PLL were finally prepared. It was noteworthy that the MALDI-FTMS result showed that no appreciable intermolecular chain transesterification happened during the ROP of L-lactide catalyzed by the DMAP. Moreover, self-assembly of these new biodegradable amphiphilic copolymers in diverse solvents were also preliminarily studied.     

Micelles based on biodegradable poly(L-glutamic acid)-b-polylactide with paramagnetic Gd ions chelated to the shell layer as a potential nanoscale MRI-visible delivery system

There is much interest in the development of a nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly( L-glutamic acid)- b-polylactide (PG- b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG- b-PLA was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring-opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly( L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)- b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r1) than a small-molecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)- b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems.     

Resilient bioresorbable copolymers based on trimethylene carbonate, L-lactide, and 1,5-dioxepan-2-one

The new combinations of monomers presented in this work were evaluated in order to create an elastic material for potential application in soft tissue engineering. Thermoplastic elastomers (TPE) of trimethylene carbonate (TMC) with L-lactide (LLA) and 1,5-dioxepan-2-one (DXO) have been synthesized using a cyclic five-membered tin alkoxide initiator. The block copolymers were designed in such a way that poly(trimethylene carbonate-co-1,5-dioxepan-2-one) formed an amorphous middle block and the poly(L-lactide) (PLLA) formed semicrystalline terminal blocks. The amorphous middle block consisted of relatively randomly distributed TMC and DXO monomer units, and the defined block structure of the PLLA terminal segments was confirmed by 13C NMR. The properties of the TMC-DXO-LLA copolymers were compared with those of triblock copolymers based either on LLA-TMC or on LLA-DXO. Differential scanning calorimetry and dynamic mechanical analysis data confirmed the micro-phase separation in the copolymers. The mechanical properties of the copolymers were evaluated using tensile testing and cycling loading. All of the copolymers synthesized showed a highly elastic behavior. The properties of copolymers could be tailored by altering the proportions of the different monomers.     

Synthesis and self-assembly of well-defined poly(amino acid) end-capped poly(ethylene glycol) and poly(2-methyl-2-oxazoline)

Poly(ethylene glycol) (PEG) and poly(2-methyl-2-oxazoline) (PMOx) are water-soluble, biocompatible polymers with stealth hemolytic activities. Poly(amino acid) (PAA) end-capped PEG and PMOx were prepared using amino-terminated derivatives of PEG and PMOx as macroinitiators for the ring-opening polymerization of γ-benzyl protected l-glutamate N-carboxyanhydride and S-benzyloxycarbonyl protected l-cysteine N-carboxyanhydride, respectively, in the presence of urea, at room temperature. The molecular weight of the PAA moiety was kept between M(n) = 2200 and 3000 g mol(-1). PMOx was polymerized by cationic ring-opening polymerization resulting in molecular weights of M(n) = 5000 and 10,000 g mol(-1), and PEG was a commercial product with M(n) = 5000 g mol(-1). Here, we investigate the self-assembly of the resulting amphiphilic block copolymers in water and the effect of the chemical structure of the block copolymers on the solution properties of self-assembled nanostructures. The PEG-block-poly(amino acid), PEG-b-PAA, and PMOx-block-poly(amino acid), PMOx-b-PAA, block copolymers have a narrow and monomodal molecular weight distribution (PDI < 1.3). Their self-assembly in water was studied by dynamic light scattering and fluorescence spectroscopy. In aqueous solution, the block copolymers associate into particles with hydrodynamic radii (R(H)) ranging in size from R(H) 70 to 130 nm, depending on the block copolymer architecture and the polymer molecular weight. Larger R(H) and critical association concentration values were obtained for copolymers containing poly(S-benzyloxycarbonyl-l-cysteine) compared to their poly(γ-benzyl-L-glutamate) analogue. FTIR investigations revealed that the poly(γ-benzyl-L-glutamate) block adopts a helical conformation, while the poly(S-benzyloxycarbonyl-L-cysteine) block exists as β-sheet.     

Block copolymerization of vinyl compounds by the terminal-group activation of poly(α-amino acids) and the characterization of block copolymers

The terminal amino groups of polysarcosine, poly(γ-benzyl l-glutamate), and poly(ε-benzyloxycarbonyl-l-lysine) were haloacetylated. The mixture of the terminally haloacetylated poly(α-amino acid) and styrene or methyl methacrylate was photoirradiated in the presence of Mn₂(CO)₁₀, or heated with Mo(CO)₆, yielding A-B-A-type block copolymers consisting of poly(α-amino acid) (the A component) and vinyl polymer (the B component). The block copolymers were characterized, and the present investigation revealed that the thermally initiated polymerization of vinyl compounds by the trichloroacetyl poly(α-amino acid)/Mo(CO)₆ system was the most suitable for the synthesis of the α-amino acid/vinyl compound block copolymers. The A-B-A type block copolymers showed higher antithrombogenicity than the corresponding homopolymers. In particular, a film of the A-B-A-type block copolymer of poly[Glu(OBzl)] and polystyrene possessed a microphase-separated structure and did not induce a conformational change of fibrinogen adsorbed, leading to a high antithrombogenicity.     

Novel synthesis of functionalized poly(3-hydroxybutanoic acid) and its copolymers.

Novel feasibility of fuctionalized poly(3-hydroxybutanoic acid), PHB, and its copolymers synthesis via ring-opening of beta-butyrolactone (ROP) mediated by activated anionic initiators or enzymes in vitro is presented. Using these new synthetic approaches, PHB with defined chemical structure of the end groups as well as block, graft and random copolymers have been obtained and characterized by IR, NMR, ESI-MS and GPC techniques. The relationship between the structure and properties of the novel polymeric materials prepared is discussed.     

Synthesis, characterization, properties, and drug release of poly(alkyl methacrylate-b-isobutylene-b-alkyl methacrylate)

Polyisobutylene (PIB)-based block copolymers have attracted significant interest as biomaterials. Poly(styrene-b-isobutylene-b-styrene) (SIBS) has been shown to be vascularly compatible and, when loaded with paclitaxel (PTx) and coated on a coronary stent, has the ability to deliver the drug directly to arterial walls. Modulation of drug release from this polymer has been achieved by varying the drug/polymer ratio, by blending SIBS with other polymers, and by derivatizing the styrene end blocks to vary the hydrophilicity of the copolymer. In this paper, results are reported on the synthesis, physical properties, and drug elution profile of PIB-based block copolymers containing methacrylate end blocks. The preparation of PIB-poly(alkyl methacrylate) block copolymers has been accomplished by a new synthetic methodology using living cationic and anionic polymerization techniques. 1,1-Diphenylethylene end-functionalized PIB was prepared from the reaction of living PIB and 1,4-bis(1-phenylethenyl)benzene, followed by the methylation of the resulting diphenyl carbenium ion with dimethylzinc (Zn(CH(3))(2)). PIB-DPE was quantitatively metalated with n-butyllithium in tetrahydrofuran, and the resulting macroinitiator could initiate the polymerization of methacrylate monomers, yielding block copolymers with high blocking efficiency. Poly(methyl methacrylate-b-isobutylene-b-methyl methacrylate) (PMMA-b-PIB-b-PMMA) and poly(hydroxyethyl methacrylate-b-isobutylene-b-hydroxyethyl methacrylate) (PHEMA-b-PIB-b-PHEMA) triblock copolymers were synthesized and used as drug delivery matrixes for coatings on coronary stents. The PMMA-b-PIB-b-PMMA/PTx system displayed zero-order drug release, while stents coated with PHEMA-b-PIB-b-PHEMA/PTx formulations exhibited a significant initial burst release of PTx. Physical characterization using atomic force microscopy and differential scanning calorimetry of the formulated PMMA-b-PIB-b-PMMA coating matrix indicated the partial miscibility of PTx with the PMMA microphase of the matrix.     

Thiol-functionalized polymeric micelles: from molecular recognition to improved mucoadhesion

Surface-modified colloids which can selectively interact with biological species or surfaces show promise as drug delivery systems. However, the preparation of such targeted devices remains challenging, especially when considering polyion complex micelles for which side reactions with the ionic core components (typically carboxylic acid or amino groups) can occur. To solve this issue, an innovative synthetic strategy is proposed and used to prepare an asymmetric poly(ethylene glycol)-block-poly(2-(N,N-dimethylamino)ethyl methacrylate) copolymer presenting a thiol group at the end of the poly(ethylene glycol) chain. Thiol groups are highly appealing given that they react almost exclusively and quantitatively with maleimides under physiological conditions, thereby facilitating the chemical functionalization of the copolymer. The simplicity of the derivatization procedure is illustrated by preparing model biotin-capped copolymers. The biotinylated copolymers are shown to self-assemble with an oligonucleotide in aqueous media to form polyion complex micelles with biotin groups at their outer surface. These micelles are capable of molecular recognition toward streptavidin. Alternatively, thiol-decorated (nonderivatized) micelles are prepared and show improved mucoadhesion through the formation of disulfide bonds with mucin. Finally, intermicellar disulfide bonds are generated under oxidative conditions to promote the formation of stimuli-responsive micellar networks.     

Synthesis of temperature-responsive heterobifunctional block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide)

Heterobifunctional block copolymers of poly(ethylene glycol) (PEG) and poly(N-isopropylacrylamide) (PNIPAM) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAM using a macromolecular trithiocarbonate PEG-based chain transfer agent. The polymerization showed all the expected features of living radical polymerization and allowed the synthesis of copolymers with different lengths of the PNIPAM block. The synthesized block copolymers contained a carboxylic acid group from L-lysine at the focal point and a trithiocarbonate group at the terminus of the PNIPAM block. The trithiocarbonate functionality was converted into a thiol group and used for conjugation of biotin to the end of the PNIPAM block. The copolymers exhibited temperature-dependent association behavior in aqueous solution with a phase transition of approximately 32 degrees C. The described heterobifunctional block copolymers show promise for surface modifications with the potential for stimulus-controlled surface presentation of ligands attached to the terminus of the PNIPAM block.     

Effect of homologous series of n-alkyl sulfates and n-alkyl trimethylammonium bromides on low molecular mass protein tyrosine phosphatase activity

The effect of anionic and cationic surfactants on acid phosphatase denaturation has been extensively studied. Low molecular mass (LMr) protein tyrosine phosphatase (PTP), a key regulatory enzyme involved in many different processes in the cell, was distinctly affected by anionic (homologous series of n-alkyl sulfates (C8-C14)) and cationic (n-alkyl trimethylammonium bromides (C12-C16)) surfactants. At concentrations 10-fold lower critical micellar concentration (cmc) values, the enzyme was completely inactivated in the presence of anionic surfactants, in a process independent of the pH, and dependent on the chain length of the surfactants. Under the same conditions, the effect of cationic surfactants on the enzyme activity was pH-dependent and only at pH 7.0 full inactivation was observed at concentrations 10-fold higher cmc values. In contrast to cationic surfactants the effect of anionic surfactants on the enzyme activity was irreversible and was not affected by the presence of NaCl. Inorganic phosphate, a known competitive inhibitor of PTP, protected the enzyme against inactivation by the surfactants. Our results suggest that the inactivation of the LMr PTP by anionic and cationic surfactants involved both electrostatic and hydrophobic interactions, and that the interactions enzyme-surfactants probably occurred at or near the active site.     

Biodegradable amphiphilic block copolymers bearing protected hydroxyl groups: synthesis and characterization

A new biodegradable amphiphilic block copolymer, poly(ethylene glycol)-b-poly(L-lactide-co-9-phenyl-2,4,8,10-tetraoxaspiro[5,5]undecan-3-one) [PEG-b-P(LA-co-PTO)], was successfully prepared by ring-opening polymerization (ROP) of L-lactide (LA) and functionalized carbonate monomer 9-phenyl-2,4,8,10-tetraozaspiro[5,5]undecan-3-one (PTO) in the presence of monohydroxyl poly(ethylene glycol) as macroinitiator using Sn(Oct)2 as catalyst. NMR, FT-IR, and GPC studies confirmed the copolymer structure. It could self-assemble into micelles in aqueous solution with critical micelle concentration (CMC) in the magnitude of mg/L, which changed with the composition of the copolymer. After catalytic hydrogenation, copolymers with active hydroxyl groups were obtained. Adhesion and proliferation of Vero cells on the copolymer films showed that the synthesized copolymers were good biocompatible materials. In vitro degradation of the copolymer before and after deprotection was investigated in the presence of proteinase K. The free hydroxyl groups on the copolymers were capable of further modification with biotin. This new amphiphilic block copolymer has great potential for both drug encapsulation and conjugate because of its low CMC and the presence of active hydroxyl groups.     

Influence of LA and GA sequence in the PLGA block on the properties of thermogelling PLGA-PEG-PLGA block copolymers

This paper reports the influence of sequence structures of block copolymers composed of poly(lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) on their thermogelling aqueous behaviors. A series of thermogelling PLGA-PEG-PLGA triblock copolymers with similar chemical compositions and block lengths but different sequences of D,L-lactide (LA) and glycolide (GA) in the PLGA block were synthesized. The difference of sequence structures arises from the different reactivities of LA and GA during the copolymerization and the transesterification after polymerization. The sol-gel transition temperature and height of gel window were found to be regulated by the sequence structure. Our study reveals that the macromolecular sequence structure influences the hydrophobic/hydrophilic balance of this kind of amphiphilic copolymers and thus alters mesoscopic micellization and the forthcoming macroscopic physical gelation in water. This finding might be helpful to guide the molecular design of the underlying thermogelling systems as injectable hydrogels.     

Poly(DMAEMA-NVP)-b-PEG-galactose as gene delivery vector for hepatocytes

A block copolymer composed of cationic polymer and poly(ethylene glycol) (PEG) was used as a DNA carrier. Poly(2-(dimethylamino)ethyl methacrylate (DMAEMA)-co-N-vinyl-2-pyrrolidone (NVP)) having a terminal carboxylic group was synthesized by free radical polymerization using an initiator, 4,4'-azobis(4-cyanovaleric acid). The terminal carboxylic acid was activated by N-hydroxysuccinimide (NHS) with dicyclohexylcarbodiimide (DCC) and then conjugated with PEG-bis(amine). For specific gene targeting to asialoglycoprotein receptor of hepatocytes, a galactose moiety was incorporated into the PEG terminal end of poly(DMAEMA-NVP)-b-PEG by reductive coupling using lactose and sodium cyanoborohydride. RSV luciferase plasmid was used as a reporter gene, and in vitro gene transfection efficiency was measured in HepG2 human hepatocarcinoma cells. Poly(DMAEMA-NVP)-b-PEG-galactose/DNA complexes formed at 0.5-2 polymer/plasmid weight ratio had compacted structures around 200 nm particle size and exhibited slightly negative surface charge. These complexes were coated with a cationic, pH sensitive, endosomolytic peptide, KALA, to generate positively charged poly(DMAEMA-NVP)-b-PEG-galactose/DNA/KALA complex particles. In the presence of serum proteins, both the PEG block and the galactose moiety of poly(DMAEMA-NVP)-b-PEG-galactose greatly enhanced the gene transfection efficiency, which was very close to that of Lipofectamine plus. Irrespective of the presence of serum proteins, as the KALA/DNA weight ratio increased, the transfection efficiency of poly(DMAEMA-NVP)-b-PEG-galactose was enhanced due to the pH dependent endosomal disruptive property of KALA. This study demonstrates that sufficient transfection efficiency as high as that of commercial agent could be attained by judicious formulation of molecular engineered poly(DMAEMA-NVP)-b-PEG-galactose in combination with an endosomolytic peptide, KALA.     

Tuning curvature and stability of monoolein bilayers by designer lipid-like peptide surfactants

This study reports the effect of loading four different charged designer lipid-like short anionic and cationic peptide surfactants on the fully hydrated monoolein (MO)-based Pn3m phase (Q(224)). The studied peptide surfactants comprise seven amino acid residues, namely A(6)D, DA(6), A(6)K, and KA(6). D (aspartic acid) bears two negative charges, K (lysine) bears one positive charge, and A (alanine) constitutes the hydrophobic tail. To elucidate the impact of these peptide surfactants, the ternary MO/peptide/water system has been investigated using small-angle X-ray scattering (SAXS), within a certain range of peptide concentrations (R相似文献   

Activation of DNA strand exchange by cationic comb-type copolymers: effect of cationic moieties of the copolymers

We have previously reported that poly(l-lysine)-graft-dextran cationic comb-type copolymers accelerate strand exchange reaction between duplex DNA and its complementary single strand by >4 orders of magnitude, while stabilizing duplex. However, the stabilization of the duplex is considered principally unfavourable for the accelerating activity since the strand exchange reaction requires, at least, partial melting of the initial duplex. Here we report the effects of different cationic moieties of cationic comb-type copolymers on the accelerating activity. The copolymer having guanidino groups exhibited markedly higher accelerating effect on strand exchange reactions than that having primary amino groups. The high accelerating effect of the former is considered to be due to its lower stabilizing effect on duplex DNA, resulting from its increased affinity to single-stranded DNA. The difference in affinity was clearly demonstrated by a fluorescence correlation spectroscopy study; the interaction of the former with single-stranded DNA still remained high even at 1 M NaCl, while that of the latter completely disappeared. These results suggest that some modes of interactions, such as hydrogen bonding, other than electrostatic interactions between the copolymers having guanidino groups and DNAs may be involved in strand exchange activation.     

Impact of silicone-based block copolymer surfactants on the surface and bulk microscopic organization of a biodegradable polymer,poly(epsilon-caprolactone)

Two amphiphilic AB block copolymers, containing a highly compatible poly(epsilon-caprolactone) (PCL) block connected to a poly(dimethylsiloxane) (PDMS) block having a low surface energy, are synthesized and characterized in terms of their dispersion in a presynthesized PCL matrix. X-ray photoelectron spectroscopy, contact angle measurements, atomic force microscopy, and optical microscopy are used to describe the evolution of the surface chemical composition, as well as the surface and bulk morphology of the PCL/copolymer blends as a function of the nature and weight surface free energy and the dispersion of the copolymers in the blends, leading to important modifications of the bulk and the surface morphology. These differences are interpreted in terms of the impact of the block copolymers on the semicrystalline polymer structure and related properties in the prospect of using the surfactants to improve the synthesis of PCL in supercritical CO(2).     

Synthesis and characterization of self-assembling block copolymers containing bioadhesive end groups

3,4-Dihydroxyphenyl-L-alanine (DOPA) is an unusual amino acid found in mussel adhesive proteins (MAPs) that is believed to lend adhesive characteristics to these proteins. In this paper, we describe a route for the conjugation of DOPA moieties to poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers. Hydroxyl end groups of PEO-PPO-PEO block copolymers were activated by N,N'-disuccinimidyl carbonate and then reacted with DOPA or its methyl ester with high coupling efficiencies from both aqueous and organic solvents. DOPA-modified PEO-PPO-PEO block copolymers were freely soluble in cold water, and dye partitioning and differential scanning calorimetry analysis of these solutions revealed that the copolymers aggregated into micelles at a characteristic temperature that was dependent on block copolymer composition and concentration in solution. Oscillatory rheometry demonstrated that above a block copolymer concentration of approximately 20 wt %, solutions of DOPA-modified PEO-PPO-PEO block copolymers exhibited sol-gel transitions upon heating. The gelation temperature could be tailored between approximately 23 and 46 degrees C by changing the composition, concentration, and molecular weight of the block copolymer. Rheological measurement of the bioadhesive interaction between DOPA-modified Pluronic and bovine submaxillary mucin indicated that DOPA-modified Pluronic was significantly more bioadhesive than unmodified Pluronic.