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PubMedDate not supplied

Imidazoles as well as thiolates in proteins bind technetium-99m.

99mTc is widely thought to directly bind proteins through thiolate groups of cysteine residues, resulting in Tc-cysteinyl-protein bonds. Chemical reduction of disulfide bonds in proteins is widely used to generate thiolates with the goal of increasing 99mTc binding. This strategy is used because most proteins contain no thiolates, but many do contain disulfide bonds. In this study, we have evaluated the hypothesis that imidazole groups of histidine are also involved in direct 99mTc binding to proteins. Human gamma-globulin was used as the model protein in these studies. The immunoglobulin was used (a) without reduction or was (b) treated with stannous ions to reduce disulfide bonds thereby increasing thiolate concentration. These proteins were used to evaluate the hypothesis that imidazole as well as thiolate groups bind Tc. The proteins were evaluated by (a) using free amino acids to compete with proteins for 99mTc and (b) by chemical modification of amino acid side chains. In addition, peptides known to contain either cysteine or histidine, but not both, were also successfully directly labeled with 99mTc. These results indicate that in proteins (and peptides) imidazole-containing groups as well as thiolate-containing groups bind Tc.

Amino Acids↗

PubMedDate not supplied

Reversible meso-scale smart polymer--protein particles of controlled sizes.

Functionalized beads and particles in the size range of tens to hundreds of nanometers (nano- to meso-scale) are finding increased applications in the bioanalytical field. We show here that conjugates of streptavidin and the temperature-responsive polymer poly(N-isopropylacrylamide) (PNIPAAm), synthesized with low polydispersities by reversible addition--fragmentation chain transfer (RAFT) polymerization, rapidly formed mesoscale polymer--protein particles above the lower critical solution temperature (LCST). The average hydrodynamic diameters of these particles could be controlled between 250 nm to 900 nm by the choice of conjugate concentration and polymer molecular weight, and/or through control of the rate of temperature change. Once formed, the biohybrid particles were found to be stable for >16 h at the controlled size, unlike the free PNIPAAm which continued to aggregate and grow over time into very large and polydisperse aggregates. The reversibility between the smart polymer--protein particles and the free polymer--protein conjugates opens potential uses in traditional diagnostic formats and in microfluidic formats where the differential diffusive and physical properties might be exploited for separations, analyte concentration, and signal generation.

Acetanilides↗

PubMedDate not supplied

Polymer-oligonucleotide conjugate synthesis from an amphiphilic block copolymer. Applications to DNA detection on microarray.

An amphiphilic block copolymer poly(tert-butylacrylamide-b-(N-acryloylmorpholine-N-acryloxysuccinimide)) (poly(TBAm-b-(NAM/NAS)) and a random copolymer poly(NAM/NAS), synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization process, have been used as support for oligonucleotide (ODN) synthesis, to elaborate polymer-oligonucleotide conjugates. In a first step, starters of ODN solid-phase synthesis were coupled to activated ester functions of polymers, and second, resulting functionalized polymers were covalently grafted onto hydroxylated controlled pore glass (CPG) support to further accomplish ODN synthesis. An efficient capping of residual hydroxyl functions of CPG was performed before synthesis, with both acetic anhydride and diethoxy-N,N-diisopropyl-phosphoramidite reagents, to suppress parasite-free ODN population present in conjugate crude material and resulting from syntheses directly initiated on silica beads. After purification, conjugates were evaluated in a DNA hybridization assay on a microarray, as macromolecules being able to favor capture of the target. Conjugate coating conditions were studied on the dT25/dA25 model. The role of the hydrophobic part (poly(TBAm)) of the conjugate synthesized with the block copolymer in the orientation of the conjugate after coating was revealed by spotting experiments achieved in a mixed solvent (DMF/H(2)O). The use of block copolymer-dT25 conjugate afforded a significant sensitivity improvement of the hybridization assay.

Amides↗

PubMedDate not supplied

Synthesis of novel poly(ethylene glycol) derivatives having pendant amino groups and aggregating behavior of its mixture with fatty acid in water.

Novel poly(ethylene glycol) (PEG) derivatives having pendant amino groups were prepared by copolymerization of allyl glycidyl ether with ethylene oxide followed by chemical modification of the double bond side chains. Dropwise addition of the mixture of monomers to the anionic initiator gave an almost monodisperse (Mw/Mn = 1.05) random copolymer. 1H NMR spectra showed that addition of 2-aminoethanethiol to the pendant allyl groups of the copolymer was completely carried out in methanol without catalyst, and an aminated PEG derivative with a definite structure was obtained. Acetylation of the pendant amino groups was readily performed by acetic anhydride with triethylamine. A gel permeation chromatogram of the acetylated polymer showed a very narrow molecular weight distribution (Mw/Mn = 1.06) of the polyamine. These cationic PEG derivatives make amphiphilic polyion complexes with fatty acids, and then aggregate in water. A fluorescence study using pyrene as a microenvironment probe revealed that the aminated PEG-lauric acid ion complex could take up the hydrophobic fluorescence probe into the lipophilic field inside, and they also had a critical aggregation concentration at [lauric acid] = 0.7 mM. It is much lower than the critical micelle concentration of the corresponding fatty acid sodium salts, indicating high stability of the polymer-fatty acid aggregate.

Carcinogens↗

PubMed2000

Interruption of the internal water chain of cytochrome f impairs photosynthetic function.

The structure of cytochrome f includes an internal chain of five water molecules and six hydrogen-bonding side chains, which are conserved throughout the phylogenetic range of photosynthetic organisms from higher plants, algae, and cyanobacteria. The in vivo electron transfer capability of Chlamydomonas reinhardtii cytochrome f was impaired in site-directed mutants of the conserved Asn and Gln residues that form hydrogen bonds with water molecules of the internal chain [Ponamarev, M. V., and Cramer, W. A. (1998) Biochemistry 37, 17199-17208]. The 251-residue extrinsic functional domain of C. reinhardtii cytochrome f was expressed in Escherichia coli without the 35 C-terminal residues of the intact cytochrome that contain the membrane anchor. Crystal structures were determined for the wild type and three "water chain" mutants (N168F, Q158L, and N153Q) having impaired photosynthetic and electron transfer function. The mutant cytochromes were produced, folded, and assembled heme at levels identical to that of the wild type in the E. coli expression system. N168F, which had a non-photosynthetic phenotype and was thus most affected by mutational substitution, also had the greatest structural perturbation with two water molecules (W4 and W5) displaced from the internal chain. Q158L, the photosynthetic mutant with the largest impairment of in vivo electron transfer, had a more weakly bound water at one position (W1). N153Q, a less impaired photosynthetic mutant, had an internal water chain with positions and hydrogen bonds identical to those of the wild type. The structure data imply that the waters of the internal chain, in addition to the surrounding protein, have a significant role in cytochrome f function.

Animals↗

PubMed1993

Interaction of phospholipase A2 with thioether amide containing phospholipid analogues.

Transferred NOE experiments have been carried out on cobra venom (Naja naja naja) phospholipase A2 (PLA2) with substrate analogues which serve as potent inhibitors. 1-(Hexylthio)-2-(hexanoylamino)-1,2-dideoxy-sn-glycero-3-pho sphoethanolamine (PE) and the corresponding phosphocholine analogue (PC) are water-soluble, short-chain, nonhydrolyzable substrate analogues which bind tightly to the enzyme. Because they are small compounds and monomeric in solution, NOEs develop inefficiently in the absence of enzyme. Thus, the PLA2/inhibitor system is ideal for analyzing transferred NOEs. The experiments are carried out under conditions that are optimal for catalysis, pH 7.5 in the presence of 2 mM CaCl2. The data show the inhibitor conformation in the catalytic site of cobra PLA2 in solution. The effect of the thioether in the sn-1 chain on the chemical shift dispersion of the methylene protons allowed for chain-specific assignments and detailed conformational analysis. Both inhibitors adopt a PLA2-bound conformation in which the end of the sn-2 chain is within 5 A of the alpha-methylene of the sn-1 chain. In addition, intermolecular contact points between the inhibitor and the enzyme were identified by NOEs.

Binding Sites↗

PubMed1992

Identification and functional importance of tyrosine sulfate residues within recombinant factor VIII.

Sulfated tyrosine residues within recombinant human factor VIII were identified by [35S]sulfate biosynthetic labeling of Chinese hamster ovary cells which express human recombinant factor VIII. Alkaline hydrolysis of purified [35S]sulfate-labeled factor VIII showed that greater than 95% of the [35S]sulfate was incorporated into tyrosine. [3H]Tyrosine and [35S]sulfate double labeling was used to quantify the presence of 6 mol of tyrosine sulfate per mole of factor VIII. Amino acid sequence analysis of thrombin and tryptic peptides isolated from [35S]sulfate-labeled factor VIII demonstrated tyrosine sulfate at residue 346 in the factor VIII heavy chain and at residues 1664 and 1680 in the factor VIII light chain. In addition, the carboxyl-terminal half of the A2 domain contained three tyrosine sulfate residues, likely at positions 718, 719, and 723. Interestingly, all sites of tyrosine sulfation border thrombin cleavage sites. The functional importance of tyrosine sulfation was examined by treatment of cells expressing factor VIII with sodium chlorate, a potent inhibitor of tyrosine sulfation. Increasing concentrations of sodium chlorate inhibited sulfate incorporation into factor VIII without affecting its synthesis and/or secretion. However, factor VIII secreted in the presence of sodium chlorate exhibited a 5-fold reduction in procoagulant activity, although the protein was susceptible to thrombin cleavage. These results suggest that tyrosine sulfation is required for full factor VIII activity and may affect the interaction of factor VIII with other components of the coagulation cascade.

Amino Acid Sequence↗

PubMed1994

Properties of the scrapie prion protein: quantitative analysis of protease resistance.

The disease-specific isoform of the prion protein (PrPSc) is an essential part of the infectious particle which causes spongiform degeneration in various mammalian species. PrPSc differs from PrP of normal animals (PrPc) by its relative protease resistance. The physical nature of this difference is still unknown. We analyzed the protease resistance of PrPSc quantitatively using an enzyme-linked immunofiltration assay. PrPSc was rendered completely protease-sensitive at alkaline pH or in > 1.5 M guanidinium thiocyanate (GdnSCN). Denaturation in 4 M GdnSCN completely abolished the protease resistance of PrPSc within 15 min, while denaturation in 7.2 M urea showed a slower time course. In the presence of ethanol, PrPSc was protected from denaturation by GdnSCN or alkaline pH. Denaturation curves were used to calculate the free energy (delta GD) as a function of different denaturant concentrations. Linear regression of delta GD values was used to extrapolate the free energy in the absence of denaturants (delta GH2O), yielding similar values (delta GH2O,GdnSCN = -2.3 kcal/mol; delta GH2O,urea = -3.1 kcal/mol). The linear relationship between delta GD and the denaturant concentration is suggestive of a two-state model involving the conformational change of a single protein domain. This is also reflected in the small number of side chains (11.6) additionally exposed to the solvent upon conversion of PrPSc to its protease-sensitive isoform. Our results suggest that only minor rearrangements of the structure of PrP are needed to abolish the protease resistance of PrPSc.

Animals↗

PubMed1993

Structural study of the sugar chains of human leukocyte common antigen CD45.

The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase and is involved in signal transduction mediated by the T cell antigen receptor. The asparagine-linked sugar chains were released as oligosaccharides from purified CD45 by hydrazinolysis. Approximately 6 mol of sugar chains was released from 1 mol of CD45. These sugar chains were converted to radioactive oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic fractions by paper electrophoresis. All of the acidic oligosaccharides were converted to neutral ones by digestion with sialidase, indicating that they are sialyl derivatives. Binding of the sialylated oligosaccharides to an SNA-agarose column as well as methylation analysis revealed that the oligosaccharides have only alpha-2,6-linked sialic acid residues. The neutral and sialidase-treated acidic oligosaccharides were fractionated by serial lectin column chromatography followed by Bio-Gel P-4 column chromatography. Structural studies of each oligosaccharide by sequential exo- and endoglycosidase digestion and by methylation analysis revealed that CD45 contains mainly bi-, tri-, and tetraantennary complex-type sugar chains. About 46% of the tetraantennary complex-type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4-branched triantennary complex-type sugar chains had the fucosyl N-acetyllactosamine group. A portion of the bi- and 2,4-branched triantennary complex-type sugar chains were bisected. In addition to these sugar chains, a small amount of high mannose-type and hybrid-type sugar chains were detected.

Asparagine↗

PubMed1983

Dimeric hemoglobin of the bivalve mollusc Anadara broughtonii: complete amino acid sequence of the globin chain.

The complete amino acid sequence of a dimeric hemoglobin (HbI) from the marine bivalve mollusc Anadara broughtonii was determined by sequencing of the intact chain and peptide fragments produced by cleavage at two asparaginylglycine bonds and at methionyl, arginyl, and tryptophanyl residues. The clam hemoglobin consists of two identical polypeptide chains. The globin chain has 146 amino acid residues with a proline at the NH2 terminus and a leucine at the COOH terminus. The calculated molecular mass of the native hemoglobin was 32945 daltons. The clam hemoglobin contains only two histidine residues, which correspond to the distal and proximal heme-linked positions. Compared with human beta chain, an additional segment of seven residues is present in the NH2-terminal region and also five less residues in the COOH-terminal region. Although such an amino-terminal elongation has been known to be characteristic of hemoglobins from the most primitive living vertebrates Cyclostomata, a very similar structure was found to occur in the hemoglobin from the primitive invertebrate arcid clam.

Amino Acid Sequence↗

PubMed1988

Molecular order and dynamics in planar lipid bilayers: effects of unsaturation and sterols.

Angle-resolved fluorescence depolarization experiments were carried out on 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) molecules embedded in macroscopically oriented multilayers of saturated [dimyristoylphosphatidylcholine (DMPC)] and unsaturated [palmitoyloleoylphosphatidylcholine (POPC), dioleoylphosphatidylcholine (DOPC), dilineoylphosphatidylcholine (DLPC), plant digalactosyldiglyceride (DGDG)] lipids with and without cholesterol. In all the lipid systems studied the order parameter (P2) of TMA-DPH molecules was found to be higher than that for DPH. Considerations of the order parameter (P4), however, indicate that DPH molecules have a heterogeneous distribution in bilayers of unsaturated lipids, with a significant fraction of the molecules lying with their long axes parallel to the bilayer planes. Both the DPH and TMA-DPH molecules exhibit a decrease in the molecular order as well as a decrease in their rates of motion on increasing the unsaturation of the hydrocarbon chains. The addition of cholesterol tends to reverse this effect, with an increase in both the order and dynamics. Bilayers of DOPC, however, exhibit a somewhat different result. It is suggested that the discrepancies between these observations and findings with lipid vesicle systems simply reflect the effects of curvature on the behavior of the probe molecules. The results indicate that the concept of membrane fluidity must be used with great caution.

Fatty Acids, Unsaturated↗

PubMed1990

Structure and chemical modifications of neurotoxin from Naja nigricollis studied by Raman spectroscopy.

Raman spectroscopy was used to determine structural features of the native toxin alpha from Naja nigricollis, which contains only one Trp and one Tyr, and of chemically modified toxins having chromophores added to these two conserved aromatic amino acids. The percentages of secondary structure were determined by using amide I polypeptidic vibration analysis and are in agreement with X-ray structure [Low et al. (1976) Proc. Natl. Acad Sci. U.S.A. 73, 2991-2994] as well as with the geometry of the disulfide bridges estimated by using the v(S-S) vibrations. In the native toxin alpha, the single invariant tyrosine 25 appears to be buried in the structure and involved in a strong hydrogen bond. We have chemically modified these two invariant aromatic side chains by addition of chromophores. The presence of a (nitrophenyl)sulfenyl (NPS) chromophore bound to the Trp does not perturb the secondary structure of the toxin as shown by the analysis of the polypeptidic amide I vibrations; however, the environment of this Trp and the geometry of a disulfide bridge seem to be modified. The secondary structure is not affected by the presence of the NPS chromophore; therefore, the decrease in binding affinity observed after modification of Trp-29 by the reagent NPS-Cl [Faure et al. (1983) Biochemistry 22, 2068-2076] is due to an alteration of the environment of this aromatic amino acid and/or a steric hindrance and not to an overall modification of the toxin structure. The binding assays of [nitrotyrosyl]toxin show that after nitration the affinity toward the monoclonal antibody M alpha 1 is unchanged and that the affinity toward the cholinergic receptor (AcChR) from Torpedo marmorata remains high. We concluded that the structure of toxin alpha after adding the NO2 chromophore to Tyr-25 is the same as it is in native toxin.

Amino Acid Sequence↗

PubMed2001

Packing is a key selection factor in the evolution of protein hydrophobic cores.

The energy derived from optimized van der Waals interactions in closely packed, folded proteins has been proposed to be of similar energetic magnitude to hydrophobicity in stabilizing the native state. If packing is this energetically important, it should influence the evolution of protein core sequences. To test this hypothesis, the occurrence of various amino acid side chains in the major hydrophobic core of staphylococcal nuclease and 42 homologous proteins was determined. Most such positions in this protein family are usually isoleucine, leucine, or valine. Previously we have constructed and measured the stabilities of 12 single, 44 double, 64 triple, and 32 quadruple mutants, representing all possible permutations of these three side chains at two overlapping sets of four positions in the core of staphylococcal nuclease. The stabilities and interaction energies of those mutants with various combinations of the most common, or consensus, sequence were compared to the stabilities of all other mutants. Mutants which had the consensus side-chain combinations were not necessarily the most stable, but usually were found to have the best interaction energies. In other words, these proteins were far more stable than would be predicted from simply summing the observed energetic effects of the component single mutations, apparently reflecting particularly favorable packing interactions that are possible for the most common side chains. An additional 12 mutants which tested possible alternate explanations of the results were constructed. The stabilities and interaction energies of these mutants also support the conclusion that packing is a crucial determinant guiding the sequence evolution of protein cores.

Amino Acid Sequence↗

PubMed2004

Influence of electric charge variation at residues 209 and 159 on the interaction of eIF4E with the mRNA 5' terminus.

Eukaryotic translation initiation factor 4E (eIF4E) is essential for efficient protein synthesis in cap-dependent translation. The protein specifically binds the cap structure at the mRNA 5' terminus and facilitates the assembly of the mRNA with other initiation factors and the 40S ribosomal subunit. Phosphorylation of eIF4E is implicated in the regulation of the initiation step of translation. However, the molecular mechanism of this regulation still remains unclear. To address this problem, we have determined the binding affinities of eIF4E specifically mutated at position 209 or 159 for a series of novel mono- and dinucleotide cap analogues by a fluorometric time-synchronized titration method. A 1.5-3-fold reduction in the affinity of cap for the S209E mutant and a 1-2-fold increase in the affinity of cap for the S209K mutant, depending on the negative charge of phosphate chains, indicate that phosphorylation at Ser209 creates electrostatic repulsion between the protein and the negatively charged cap structure. The inhibition of the ability to bind cap analogues by the K159A mutant and its phosphorylated counterpart shows significant participation of Lys159 in the binding of the capped mRNA. Both structural modifications, phosphorylation and the replacement of lysine with alanine, result in an increase in the negative Gibbs free energy of association that is proportional to the length of the cap phosphate chain and additive, i.e., equal to the sum of the individual destabilizing changes of DeltaG degrees. The possible implication of these results for the mechanism of control of eIF4E by phosphorylation, especially for the "clamping model", is discussed.

Alanine↗

PubMed1996

The three-dimensional solution structure of the SH2 domain from p55blk kinase.

Signal transduction in B cells is mediated, in part, by the interaction of the cytoplasmic components of the antigen receptor complex and various members of the src family tyrosine kinases. Key to this process appears to be the interaction of the tyrosine kinase SH2 domains with the tyrosine-phosphorylated cytoplasmic domain of Ig-alpha, a disulfide-bonded heterodimeric (with Ig-beta or Ig-gamma) transmembrane protein that noncovalently associates with the antigen receptor immunoglobin chains. In addition to binding to the phosphorylated cytoplasmic domains of Ig-alpha and Ig-beta, blk and fyn(T), two members of the src family kinases, have been shown to bind overlapping but distinct sets of phosphoproteins [Malek & Desiderio (1993) J. Biol. Chem. 268. 22557-22565]. A comparison of their three-dimensional structures may elucidate the apparently subtle differences required for phosphoprotein discrimination. To begin characterizing the blk/fyn/phosphosphoprotein interactions, we have determined the three-dimensional solution structure of the SH2 domain of blk kinase by nuclear magnetic resonance (NMR) spectroscopy. 1H, 13C, and 15N resonances of the SH2 domain of blk kinase were assigned by analysis of multidimensional, double- and triple-resonance NMR experiments. Twenty structures of the blk SH2 domain were refined with the program X-PLOR using a total of 2080 experimentally derived conformational restraints. The structures converged to a root-mean-squared (rms) distance deviation of 0.51 and 0.95 A for the backbone atoms and for the non-hydrogen atoms, respectively. The blk SH2 domain adopts the prototypical SH2 fold. Structurally, blk SH2 is most similar to the crystal structure of the v-src SH2 domain [Waksman et al. (1993) Nature 358.646-653] and superimposes on the crystal structure with an rmsd of 1.52 A for the backbone atoms. The largest deviations occur in the four loops interconnecting beta-strands A-E, which are the least well-defined regions in the NMR structure. Exclusion of these loops lowers this rmsd to 0.82 A. The conformation of the BC loop in the blk SH2 domain is similar to the open conformation in the apo lck SH2 domain, suggesting that, like the lck SH2 domain, the blk SH2 domain may have a gated phosphopeptide binding site. Finally, it is proposed that the amino acid substitution of Lys 88 (blk) for Glu [fyn(T)] is important for the observed differences in specificity between blk and fyn(T) SH2 domains.

Amino Acid Sequence↗

PubMed1997

Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors.

In cell cultures, the key residues associated with HIV-1 resistance to cyclic urea-based HIV-1 protease (PR) inhibitors are Val82 and Ile84 of HIV-1 PR. To gain an understanding of how these two residues modulate inhibitor binding, we have measured the Ki values of three recombinant mutant proteases, I84V, V82F, and V82F/I84V, for DMP323 and DMP450, and determined the three-dimensional structures of their complexes to 2.1-1.9 A resolution with R factors of 18.7-19.6%. The Ki values of these mutants increased by 25-, 0.5-, and 1000-fold compared to the wild-type values of 0.8 and 0.4 nM for DMP323 and DMP450, respectively. The wild-type and mutant complexes overall are very similar (rms deviations of 0.2-0.3 A) except for differences in the patterns of their van der Waals (vdw) interactions, which appear to modulate the Ki values of the mutants. The loss of the CD1 atom of Ile84, in the I84V mutant complexes, creates a hole in the S1 subsite, reducing the number of vdw contacts and increasing the Ki values. The V82F mutant binds DMP323 more tightly than wild type because the side chain of Phe82 forms additional vdw and edge-to-face interactions with the P1 group of DMP323. The Ki values of the single mutants are not additive because the side chain of Phe82 rotates out of the S1 subsite in the double mutant (the chi 1 angles of Phe82 and -182 in the V82F and V82F/I84V mutants differ by 90 and 185 degrees, respectively), further reducing the vdw interactions. Finally, compensatory shifts in the I84V and V82F/ I84V complexes pick up a small number of new contacts, but too few to offset the initial loss of interactions caused by the mutations. Therefore, our data suggest that variants persist in the presence of DMP323 and DMP450 because of a decrease in vdw interactions between the mutant proteases and inhibitors.

Azepines↗

PubMedDate not supplied

Synthesis of well-defined amphiphilic block copolymers having phospholipid polymer sequences as a novel biocompatible polymer micelle reagent.

To realize safer and effective drug administration, novel well-defined and biocompatible amphiphilic block copolymers containing phospholipid polymer sequences were synthesized. At first, the homopolymer of 2-methacryloyloxyethylphosphorylcholine (MPC) was synthesized in water by reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization. The "living" polymerization was confirmed by the fact that the number-average molecular weight increased linearly with monomer conversion while the molecular weight distribution remained narrow independent of the conversion. The poly(MPC) thus prepared is end-capped with a dithioester moiety. Using the dithioester-capped poly(MPC) as a macro chain transfer agent, AB diblock copolymers of MPC and n-butyl methacrylate (BMA) were synthesized. Associative properties of the amphiphilic block copolymer (pMPC(m)-BMA(n)) with varying poly(BMA) block lengths were investigated using NMR, fluorescence probe, static light scattering (SLS), and quasi-elastic light scattering (QELS) techniques. Proton NMR data in D2O indicated highly restricted motions of the n-butyl moieties, arising from hydrophobic associations of poly(BMA) blocks. Fluorescence spectra of N-phenyl-1-naphthylamine indicated that the probes were solubilized in the polymer micelles in water. The formation of polymer micelles comprising a core with poly(BMA) blocks and shell with hydrophilic poly(MPC) blocks was suggested by SLS and QELS data. The size and mass of the micelle increased with increasing poly(BMA) block length. With an expectation of a pharmaceutical application of pMPC(m)-BMA(n), solubilization of a poorly water-soluble anticancer agent, paclitaxel (PTX), was investigated. PTX dissolved well in aqueous solutions of pMPC(m)-BMA(n) as compared with pure water, implying that PTX is incorporated into the hydrophobic core of the polymer micelle. Since excellent biocompatible poly(MPC) sequences form an outer shell of the micelle, pMPC(m)-BMA(n) may find application as a promising reagent to make a good formulation with a hydrophobic drug.

Antineoplastic Agents↗

PubMed2006

Synthesis of various glycopolymer architectures via RAFT polymerization: from block copolymers to stars.

Well-defined linear poly(acryloyl glucosamine) (PAGA) exhibiting molar masses ranging from 3 to 120 K and low polydispersities have been prepared via reversible addition-fragmentation chain transfer polymerization (RAFT) in aqueous solution without recourse to protecting group chemistry. The livingness of the process was further demonstrated by successfully chain-extending one of these polymers with N-isopropylacrylamide affording narrow dispersed thermosensitive diblocks. This strategy of polymerization was finally extended to the preparation of glycopolymer stars from Z designed non-water-soluble trifunctional RAFT agent. After the growth of very short blocks of poly(hydroxyethyl acrylate) ((-)DP(n)(branch) = 10), AGA was polymerized in aqueous solution in a controlled manner affording well-defined 3-arm glycopolymer stars.

Acrylamides↗