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Crystals of the title compound [systematic name: (2R)-tert-butyl N-(1,3-dihydroxy-3-methyl-2-butyl)carbamate], C10H21NO4, were successfully grown from an ethyl ­acetate solution. There is one independent mol­ecule in the asymmetric unit. The urethane linkage, –O—CO—NH–, is a cis conformer and the mol­ecules are linked into a dimer by two N—H⋯O=C hydrogen bonds. The dimers are connected together by O—H⋯O hydrogen bonds in which four hydroxy groups are involved.

Crystals of the title compound, C16H30N2O5, were successfully grown from an ethyl acetate solution. There are two independent mol­ecules in the asymmetric unit. One mol­ecule has a cis and the other a trans conformation at the urethane linkage, –O—CO—NH–. Independent mol­ecules are linked into chains by NH⋯O=C and OH⋯O=C hydrogen bonds along the c axis.

Crystals of the title compound, C17H30N2O7, were successfully grown from ethyl ­acetate at room temperature. In the crystal structure, a free carboxyl­ic acid group is found at the terminal C atom. The free acid —OH group contributes to a hydrogen-bond network, together with two N—H⋯O interactions, forming tight packing.

Six new sequential hydrophobic polypeptides consisting of leucyl and isoleucyl residues were synthesized by polycondensation of peptide active esters. Solid samples of these polypeptides were obtained by fast reprecipitation from a solution in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) or HFIP/dichloroacetic acid with diethyl ether. The conformation of the solid sample was determined by IR spectroscopy as follows : the β-structure for (Leu-Ile-Ile-Leu) n , a mixture of the β-structure and α-helix for (Leu-Ile-Leu) n , and the α-helix for (Ala-Ile-Ile-Leu) n , (-Leu-lle-Ile-Leu) n , (Leu-Ile-lle-Gly) n , and (Leu-Ile-Ile-Aib) n . The factor governing the specification of the β-structure/α-helix was deduced to be the consecutiveness of the tidily aligned hydrophobic side chains of the amino acid residues to afford sterically well-regulated intermolecular aggregation of the polypeptides prior to the conformational preference of the individual amino acid residue.

The T 2 spin-spin relaxation time curves were used to monitor the network formation during the radiation-induced polymerization of N-isopropylacrylamide (NIPAAm) in solution. Before irradiation, a single long exponential decay curve is observed (T 2L , about 1 sec). After irradiation with doses in the range of 0.03 – 0.1 kGy, T 2L decreases to about 100 msec, and there appears a shorter component, T 2S , of the order of tens of milliseconds, indicating the presence of a network. From solubility measurements the gel dose was 71 Gy. At doses above 0.1 kGy the decay curve always consist of two components, a longer of the order of tens of millisecons, and a shorter of the order of milliseconds. The temperature dependence of the relaxation time for samples irradiated with different doses is in good agreement with swelling data.

New functional microspheres consisting of diethylene glycol dimethacrylate (2G) and a methacryloyl monomer containing four amino acids, l-asparagynyl-l-alanyl-l-asparagynyll-proline methyl ester (MA-NANPOMe) were synthesized by radiation induced co-polymerization. These four amino acids were previously identified as a part of the immunodominant region of the circumsporozoite (CS) protein of Plasmodium falciparum. The use of this synthetic peptide as an antigen in immunoassay for malaria is promising: the microspheres exposed to the sera of malaria patients showed marked fluorescence, while the spheres contacted with sera of healthy donors showed no fluorescence.

Several types of copolymers of CR-39 were prepared to find its usefulness as a nuclear track detector of high sensitivity. Track responses of these copolymers were investigated by irradiating energetic ions from proton through Ar. The copolymer of CR-39 monomer with N-isopropylacrylamide (NIPAAm) shows higher sensitivity than that of pure CR-39 for low LET particles such as protons. Preliminary results are reported for the track responses of copolymers (CR-39/NIPAAm) with various contents of NIPAAm as well as the etching properties.

Crystals of the title compound, C16H28N2O7, were successfully grown from an oily product at low temperature (below 260 K). There are two independent mol­ecules in the asymmetric unit. One mol­ecule has a cis and the other a trans conformation at the urethane linkage, —O—CO—NH—. Independent mol­ecules are linked into dimers, but not into chains, by N—H⋯O=C hydrogen bonds.

Loosely cross-linked poly(methacryloyl- DL -alanine methyl ester, MA- DL -AlaOme) gels, which were prepared by radiation-induced polymerization, exhibited a reversible low-temperature swelling and high-temperature deswelling when cycled in water at different temperatures at 24-h intervals, in the range of 0 and 40°C. The thermo-response strongly depended upon irradiation condition. Increasing the irradiation dose resulted in a formation of lower molecular weight polymer owing to the scission of polymer chain, in which it gave a high swelling ability at low temperature, in contrast to a sluggish shrinkage at high temperature. On the other hand, no irradiation temperature affects the thermo-response of the gel. An important characteristic of the MA- DL -AlaOMe polymer gel is the formation of the membrane barrier at the surface with the rise in temperature, but it disappears in reswelling, to be termed “surface-controlling on-off switch system”. Brilliant blue FCF (BB) as a model compound was corporated into the gel to evaluate the capability as a thermo-responsive carrier for application in drug delivery systems, and it was found that the reversibly surface-controlling on-off switch function responsible to temperature changes plays an important role in a pulsatile release of BB of BB from the gel in vivo .

Hydrophobic styrene (St) was copolymerized with acryloyl- l -proline methyl ester (A-ProOMe) known as a characteristic thermo-responsive gel. The thermo-responsive function of this copolymer gel perfectly disappeared by the introduction of St > 20 mol% in the gel because of a strongly hydrophobic effect owing to pendant phenyl moiety. On thermo-responsive copolymer gels ranging in St composition from 1 to 10 mol%, the deswelling process proceeded faster than swelling process. This difference was explained from the results of activation energies (|ΔE|). The swelling-temperature curve of such a thermo-responsive gel was tried to investigate by a statistical moment analysis, e.g. the area under swelling-temperature curve (AUC), mean swelling transition temperature (MSTT), and variance of swelling transition temperature (VSTT), suggesting that these values corresponds very closely to St composition in the gel. 9-β- d -arabinofuranosyladenine (Ara-A) was incorporated into the thermoresponsive copoly(A-ProOMe/St) gels and, as a result, it was found that the in vitro release of Ara-A from the gel when cycled at different temperatures at 60-min intervals shows a typical pulsatile release such as a slight amount of drug release at 10°C and a good deal of drug release at 30°C.

Acryloyl-L-prolylamide (1b) and its two simple derivatives, acryloyl-L-prolyl-N′, N′-dimethylamide (1a) and acryloyl-L-prolyl-N′-methylamide (1c), were synthesized for the first time.

Photografting of N-isopropylacrylamide (NIPAAm) on ethylene–vinyl alcohol copolymer films (thickness = 15,20, and 25 μm) and low-and high-density polyethylene films (thickness = 30 μm) was carried out at 60°C in a water medium. Xanthone was used as a photoinitiator by coating it on the film samples. The resultant NIPAAm-grafted films exhibited a temperature-responsive character, which was evaluated by measuring a dimensional change of the grafted films. The grafted films swelled and shrank in water at temperatures lower and higher than around 30°C, respectively. The character was found to be reversible between 0 and 50°C. It was observed that the extent of the character is largely influenced by film thickness, location of NIPAAm-grafted chains, and crystallinity of film substrate. © 1994 John Wiley & Sons, Inc.

Loosely cross-linked polymer gels consisting of acryloyl- L -proline methyl ester (A-ProOMe), 2-hydroxyethyl methacrylate (HEMA), and polyethylene glycol dimethacrylate (nG) were synthesized by radiation-induced polymerization, using γ-rays from a 60Co source. The percent swelling behavior of the gels obtained was examined in water in the range of 0–50°C, showing that gels exhibit a characteristic thermo-response such as low-temperature swelling and high-temperature deswelling, depending strongly upon monomer composition. 9-β- D -Arabinofuranosyladenine was incorporated into this polymer gel to evaluate the pulsatile drug release when cycled at 10 and 37°C, in which the drug release kinetics could be explained by a matrix pumping mechanism.

The loosely cross-linked poly(acryloyl-L-proline methyl ester) gel, which is known as one of the typical thermo-responsive gels, shows a volume transition around approximately 14°C in pure water. This volume transition is shifted to higher temperature by treatment in aqueous sodium dodecyl sulfate (SDS). The analysis of the swelling-temperature curve (frequency distribution) was performed according to a moment analysis, in which the area under the swelling-temperature curve (AUC), mean swelling transition temperature (MSTT) and variance of swelling transition temperature (VSTT) were calculated. It is shown that the apparent volume transition temperature can be estimated from MSTT and that VSTT can be used to characterize the shape of the corresponding curves.

Uncross-linked acryloyl-L-proline methyl ester (A-ProOMe) polymer, which was obtained by irradiating up to 30 kGy at 25°C using γ-rays from a 6°Co source, showed a coil-globule transition in water around a lower critical solution temperature (LCST) of approximately 14°C. From results of light-scattering measurements, it was found that the molecular weight (Mw) of the polymer was 964,000 at 4°C, 1,270,000 at 10°C, 56,100,000 at 20°C, 82,200,000 at 35°C, and 98,200,000 at 50°C in water, in contrast to 41, 40, 20, 10, and 8 nm in the above order for the particle radius of gyration ( 2>½), in which the pendant ProOMe group with cis-form might occur in big clusters above the LCST temperature. Cross-linked homopolymers were obtained with irradiation at doses more than 80 kGy at 25°C. The results of electron spin resonance (ESR) measurements showed that the formation of cross-linked poly(A-ProOMe) gels is due to the bridging of neighbor ing ProOMe groups. Even after cross-linking, the gels obtained gave characteristic thermo- responses, such as low-temperature swelling and high-temperature deswelling in water.

Ion track grafting enables the manufacture of chemically responsive track pores analogous to the discrete membrane channels found in biology. For this purpose etched ion tracks generated in CR-39 are surface-grafted by methacryloyl-L-alaninemethylester. In the future, the responsive track pores could be used to model the actively controlled channels in biomembranes and may lead to interesting technological applications.

Acryloyl-L-prolylamide (1b) and its two simple derivatives, acryloyl-L-prolyl-N′, N′-dimethylamide (1a) and acryloyl-L-prolyl-N′-methylamide (1c), were synthesized for the first time.

The practical synthetic method for a series of substantially novel fluorine-containing polyfunctional aromatic compounds, 3-trifluoromethyl-4-halobenzonitriles [halo = Cl, Br, and F], was established by using copper-cyano complexes as effective Sandmeyer cyanating reagents.

Novel cyclodextrin dimers (1, 2, 3 and 4) whose cyclodextrins were linked with sulfur-containing linkers, namely a thiodipropanamide, a dithiodipropanamide, a thiodiethanamide, or a dithiodiethanamide linker, were synthesized by a reaction of 6-amino-6-deoxycycloheptaose 7 with the corresponding dicarboxylic acids. For their preparation, dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate were examined as coupling reagents. 1H NMR studies of the dimers suggested an intramolecular inclusion of the linker moiety to the cyclodextrin cavity, which affected the complexation of guest molecules. Dimer 4 was converted to another type of dimer 5 by reductive cleavage of the disulfide bond to generate thiol group-containing monomeric species followed by a substitution reaction with 6-O-tosyl derivative 6.

Three isomers of cyclomaltoheptaose derivatives, 1a–c, which possess five mesitylenesulfonyloxy groups on their C-6 atoms, were prepared. Assignment of the regiosiomers was performed by their conversion into compounds containing five 3,6-anhydroglucose units followed by 1H NMR analyses. The structures of the pentakis(3,6-anhydro) derivatives were also confirmed by their derivation from the known bis(TBDMS) derivatives.

Poly(acryloyl- l -proline methyl ester) (A-ProOMe) obtained by radiation-induced polymerization exhibited a lower critical solution temperature (LCST) at ca 14°C. Physical properties such as molecular weight ( M W ), particle radius of gyration ( 〈S 2 〉 1 2 ), and particle size distribution were investigated by static and dynamic light-scattering measurements as a function of temperature. The M W of poly (A-ProOMe), obtained by irradiating up to 30 kGy at 25°C, increased from 1,270,000 at 10°C to 56,100,000 at 20°C in water; on the other hand, the 〈S 2 〉 1 2 value decreased with rise in temperature, e.g. from 40.5 to 20.1 nm between 10 and 20°C. From the results of particle size distribution, it was concluded that polymers, dissolved in water below the LCST, aggregate to make globules above LCST.

New methacryloyldipeptides having the sequences of l -alanyl-glycine ethyl ester (Ala-Gly-OEt), l -valyl-glycine ethyl ester (Val-Gly-OEt), l -leucyl-glycine ethyl ester (Leu-Gly-OEt), and l -isoleucyl-glycine ethyl ester (ILe-Gly-OEt) as side chains were synthesized to evaluate environmental response of its polymer hydrogels, especially solvent and temperature. The swelling values of each hydrogel were reached maximally in a 30/70 vol% water/2-propanol mixture at 10°C, at which the degree of gel swelling v markedly distinct from kind of pendant group, increasing in that order Ile-Gly-OEt>Leu-Gly-OEt>Val-Gly-OEt. The temperature-response was examined for a poly(methacryloyl-ILe-Gly-OEt) hydrogelin the above binary solvent system and it was found that the hydrogel gives a reversible low-temperature-swelling and high-temperature-deswelling.

Biodegradable polydepsipeptides having the sequences of l -alanyl- l -amino acyl-γ-ethyl l -glutamyl- l -hydroxy acyl [Ala-AA-Glu(OEt)-HA] were synthesized to evaluate the hydrolysis of the specimens by the action of enzymes. The enzymatic degradation and its degradation pattern were strongly dependent on the difference in size of side chain residues of l -aminoacyl and l -hydroxyacyl units in the sequence and, as a result, it was found that the introduction of l -leucic acid (Hmp) as HA unit in an Ala-Ala-Clu(OEt)-HA sequence leads to a typical S-type degradation pattern, in contrast to a parabolic-type for the introduction of glycolic acid (Hea). From the difference in action of enzymes, it was concluded that the sequential polydepsipeptides are much more subject to hydrolysis by esterase-type enzymes rather than by protease-type enzymes. For comparison, the in vivo degradation was examined; it depended strongly on the site of implantation, and degrading to the greatest extent when implanted in the kidney. Microscopic observation showed that the degradation occurs heterogeneously at the surface of the specimen with formation of micropores.

Methacryloyldipeptides having sequences of l -amino acyl- l -alanine ethyl esters (AA-Ala-OEt) as pendant groups which were synthesized by the cyclohexylcarbodiimide-mediated condensation method, were polymerized in the presence of catalysts, to evaluate their capabilities as new external stimulus-responsive hydrogels. The hydrogels exhibited a reversible response for temperature change, e.g. low-temperature swelling and high-temperature deswelling in a water-methanol system, especially for methanol contents exceeding 50 vol%. The resulting temperature-response increased in the order Gly-Ala-OEt (Gly:glycine)Ala-Ala-OEt Val-Ala-OEt (Val: l -valine)ILe-Ala-OEt (ILe: l -isoleucine) as pendant groups.

Methacryloyl- L -alanine derivatives having various carboxyl-protecting groups, for example, hydrogen, methyl, ethyl and benzyl groups, were synthesized by reacting L -alanine ester hydrochlorides with methacrylic acid in the presence of triethylamine, by a so-called dicyclohexylcarbodiimide-mediated condensation method. These polymer hydrogels showed a typical thermo-response such as low-temperature-swelling and high-temperature-deswelling, in water, in the range of 0–40°C. Such a response was characterized with regard to kind of carboxyl-protecting group in the hydrogel.

Methacryloyl-D-alanine methyl ester (MA-D-AlaOMe) and methacryloyl-L-alanine methyl ester (MA-L-AlaOMe) were synthesized and polymerized by irradiation using γ-rays from a 60Co source, in order to investigate the effect of optical isomerism on the swelling of homopolymer hydrogels which changes in temperature in water. These hydrogels showed a typical thermo-response such as low-temperature-swelling and high-temperature-deswelling, but no difference in swelling between the two hydrogels could be regarded as significant. The stable swelling-deswelling kinetics on repeated use are characterized by very limited temperature ranges (0–40°C), and above this range (for example, when cycled between 10 and 70°C) the reversible thermo-response perfectly disappeared because of gel collapse. This defect could be overcome by copolymerization with other functional monomers and the resulting copolymers exhibited a reversible thermostability superior to those of homopolymers of MA-D-AlaOMe and MA-L-AlaOMe, depending strongly upon the type of copolymer and its composition. The hydrolysis products of these hydrogels gave a reversible-response not only for temperature but also for pH. The swelling-deswelling kinetics of non-hydrolyzed and hydrolyzed hydrogels were characterized with regard to porous structure formed in the hydrogel.

A combinatorial peptide library contains an enormous combination of amino acid sequences and drug candidates, but an effective screening strategy to identify a variety of bioactive peptides has yet to be established. In this article, a random hexapeptide library was screened to identify novel peptide ligands for a 5-oxo-ETE receptor (OXER), which is a G-protein-coupled receptor for bioactive lipids, by using an OXER-Gi1alpha fusion protein. We successfully identified 2 hexapeptides-Ac-HMQLYF-NH2 and Ac-HMWLYF-NH(2)-that exhibited agonistic activity. Although the corresponding affinities were relatively low (EC50 values of 146 and 6.7 microM, respectively), the activities were confirmed by other independent cell-based assay methods, namely, intracellular calcium mobilization and cell chemotaxis. This study demonstrates that a combinatorial peptide library may be screened using a [35S]GTPgammaS binding assay with G-protein-coupled receptor (GPCR)-Galpha fusion proteins, in general, and that of peptide ligands can be obtained even for nonpeptide receptors.

Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L-alanyl)n-gamma-ethyl L-glutamyl-L-lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n-Glu(OEt)-Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n-Glu(OEt)-Lac]. The resulting poly(Ala-Ala-Glu(OEt)-Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing-hormone-releasing hormone agonist des-Gly10-[D-Leu6]-LH-RH ethylamide (LH-RH agonist), was incorporated into a sequential poly(Ala-Ala-Glu(OEt)-Lac) carrier by the melt-pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend-type and sandwich-type formulations. The rate of in vivo release of LH-RH agonist from a blend-type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwich-type formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 +/- 14 micrograms/day).

A sequential polydepsipeptide containing a tripeptide sequence L-alanyl-Lalanylγ-ethyl L-glutamyl and anα-hydroxy acid L-lactic acid, poly(Ala-Ala-Glu(OEt)-Lac), was synthesized to prepare the microspherical particles by the solvent evaporation process. In this case, the solvents play the most important role for the preparation of polydepsipeptide microspheres and, as an example, when 200 mg of the polydepsipeptide dissolved in 10 ml of 98/2% chloroform/dichloroacetic acid mixture was stirred at 400 rpm and 30 ‡C, the microspherical particles with mean diameter of 58Μm were formed after pouring into 200 ml of 1% (w/v) poly(vinyl alcohol) solution. 17Β-Estradiol was incorporated into the particles, and the resulting particles were found to contain 5 mg of drug per 25 mg of the particle. The in vivo release of drug from the microspherical formulation was evaluated by measuring the pharmacological influence on rat prostate. It was found that the sufficient amount of drug, keeping the effective pharmacological influence, is supplied during the first 12-week period, followed by an incomplete supplying of drug intil the implant is perfectly degraded in vivo in the 25th week from the start of implantation.

L'etude de la degradation in vitro par la trypsine et la lipase et in vitro dans le rat montre que la biodegradation est la plus rapide pour le polymere [(NH-CH(CH 3 )-CO)-(O-CH(CH 3 )-CO)] n

The depsipeptides Boc-Leu-Lac-OEt (1) and Boc-(Leu-Leu-Lac)(n)-OEt (n = 1, 2) (2 and 3, respectively) (Boc = tert-butyloxycarbonyl, Lac = L-lactic acid residue) has been synthesized and studied by crystallographic, CD spectroscopic, and ESI-MS analyses. In the packing cells, those three compounds adopt beta-strand conformations. Each molecule is linked into a dimer (1) or an infinite assembly (2 and 3) by tight hydrogen bonds of the type NH...O==C. Interestingly, the hexamer, 3 shows the first example of antiparallel pleated beta-sheet crystal structure for a depsipeptide molecule. In the packing cells, especially for 3, the ester groups O--C==O are perpendicularly oriented to the amide groups NH--C==O and beta-sheet planes to avoid the interaction between --O--(ester) and O==C. Therefore, when the chain length become longer, the O...O==C repulsion interaction works as a beta-sheet breaker and hence promotes an alpha-helical structure as observed for Boc-(Leu-Leu-Lac)(3)-Leu-Leu-OEt (4) (Oku et al. Biopolymers 2004, 75, 242-254) and Boc-(Leu-Leu-Lac)(n)-OEt (n = 4-6) (5-7) (Katakai et al., Biopolymers 1996, 38, 285-290), in which the O...O==C repulsion does not cause significant structural changes in alpha-helical main chains. Therefore from the structural and spectroscopic analyses, we have found governing factors for the specificity in the beta-sheet and alpha-helix decision in this series of depsipeptides, -(Leu-Leu-Lac)(n)-.

We synthesized gels by a simultaneous radiation-induced polymerization and crosslinking of acryloyl- and methacryloylproline methyl ester in aqueous solution without any crosslinker. We call these gels selfd-bridged gels. Their different swelling behavior originates in the different microstructures which is the result of the different mechanisms of polymerization and cross-linking for these two monomers

The depsipeptide Boc(1)-Leu(2)-Leu(3)-Ala(4)-Leu(5)-Leu(6)-Lac(7)-Leu(8)-Leu(9)-Lac(10)-Leu(11)-Leu(12)-Lac(13)-Leu(14)-Leu(15)-OEt(16) (1) (Boc = tert-butyloxycarbonyl, Lac = L-lactic acid residue) has been synthesized from the peptide Boc-Leu-Leu-Ala-OEt (2) and a depsipeptide, Boc-(Leu-Leu-Lac)(3)-Leu-Leu-OEt (3). Single crystals of 1 were successfully obtained and the structure has been solved by direct methods (such as Sir2002 and Shake-and-Bake). Interestingly, 1 adopts an alpha/3(10)-conjugated helix containing a kink at the junction of peptide and depsipeptide segments, Leu3-Lac7. This is significantly different from the conformation of 3, which has a straight alpha-helical structure with standard phi and psi angles. Microcrystalline CD spectra were also studied to compare structural properties of 1 and 3. The differences between alpha/3(10)- and alpha-helices appear in these CD spectra.

The swelling behavior of acryloyl- l -proline methyl ester (A-ProOMe) gel with a reversible and stepwise volume change was studied in aqueous solutions containing sodium dodecyl sulfate (SDS) and lithium dodecyl sulfate (LDS). The transition temperature was evaluated from both the midpoint of the slope under the swelling vs temperature curve (VPTT) and the statistical moment analysis using an area under the curve (ISTT). With the addition of surfactants, the VPTT and ISTT increased and, as a result, it was found that no changes in transition temperature are influenced by the difference between the counterions of the two surfactants. A plot of VPTT and ISTT gave a straight line with a reasonable correlation, suggesting that the transition temperature of the gel, which is affected by surfactant concentration, can be evaluated from ISTT.

Hydrophilic 2-hydroxyethyl methacrylate (HEMA) and hydrophobic styrene (St) were introduced into a thermo-responsive gel of acryloyl- l -proline methyl ester (A-ProOMe) by means of radiation-induced copolymerization in the presence of a slight amount of crosslinker. The copolymer gels showed a reversible volume phase transition around 14°C and, as a result, it was found that the introduction of HEMA and St leads to the formation of a ‘matrix pumping’ gel which is characterized by a rapid shrinkage of the whole matrix without the disappearance of pores in the initial stageof deswelling. Such a thermo-responsive function appeared in limited composition ranges; 0–90 mol% HEMA and 0–50 mol% St. 9-β- d -Arabinofuranosyladenine (Ara-A) was incorporated into the A-ProOMe-containing gel to evaluate the release behavior of Ara-A when cycled between 10 and 37°C. The drug resulted in a pulsatile release consisting of a slight amount of drug release at 10°C and a good deal of drug release at 37°C, in closely relation to a matrix pumping mechanism.

An X-ray crystallographic analysis of the bis-Ndelta-Boc-tetra-Nalpha-methyl derivative of gramicidin S, cyclo(-Val-MeOrn(Boc)-Leu-d-MePhe-Pro-)2, was undertaken successfully (R-factor = 0.088). As expected, the main chain adopts an antiparallel pleated beta-sheet conformation, but the pleated sheet is slightly twisted, and the sense of twisting is opposite to that found in the reported crystal structures of the gramicidin S-urea complex and the bis-Ndelta-(trichloroacetyl) and bis-Ndelta-(m-bromobenzoyl) derivatives of gramicidin S. In agreement with the observed resistance toward N-methylation, the urethane NH groups of the protected Orn side chains are hydrogen bonded to the carbonyl groups of the d-Phe residues. However, the side-chain-main-chain hydrogen bonding is in the i --i - 3 mode, although hydrogen bonding in the i --i + 2 mode was deduced from a 1H NMR study of protected gramicidin S derivatives and was actually found in the crystal structures of the diacylated gramicidin S.

Poly(N-isopropylacrylamide) hydrogels have been synthesized by a new method of radiation-induced simultaneous polymerization and cross-linking of an aqueous solution of the monomer without any additive. Below LCST, the gels synthesized by lower doses swell to a higher extent than the more cross-linked gels. Above LCST, the swelling percentage increased until about 50 kGy and then decreased with increasing the dose

Swelling of methacryloyl polymer gels [CH 2 C(CH 3 )(CONHCHRCOOR')] n (R= CH 3 , R'= H, Me, Et, t-Bu, CH 2 Ph; R'= Me, R= H, Me, i-Pr, CH(Me)Et) was investigated as a function of temperature and time

In order to clarify the relationship between the crosslinked structure of thermo-responsive polymer and drug release profile, polymer gels based on acryloyl-L-proline methyl ester (A-ProOMe) were synthesized in a mixture of water and acetone by the following two methods: a simultaneously occurring process of radiation-induced polymerization and crosslinking without a crosslinker (self-bridging method), and radiation-induced polymerization in the presence of the crosslinker tetradecaethylene glycol dimethacrylate (crosslinker method). The pronounced gap in thermo-response between two A-ProOMe gels, with an apparent degree of crosslinking of 11 for 1-propanol, shows a different shrinking pattern in the initial stage of time. The gels, which were obtained with the self-bridging method and the crosslinker method, were kept constant at a swelling ratio of 17 in water at 0 degree C for all systems. However, those values fell to 0.5 and 4, respectively, at 10 min after the temperature was increased to 37 degrees C. The release mechanism of ketoprofen from two gel devices showed an anomalous (non-Fickian) transport, in which the release of ketoprofen with a low water-solubility could be directly related to the rapid release of water accompanying a gel shrinkage.

Thermosensitive hydrogels were obtained by radiation-induced polymerization of acryloyl- l -proline methyl ester in the presence of a crosslinking agent. The measurements of equilibrium water content in the temperature range between 0° and 60°C showed that the samples swelled at low temperatures while they shrank at high temperatures. These hydrogels were used as drug delivery systems for the controlled release of insulin. In vivo studies carried out on diabetic rats ascertained a significant reduction in the hyperglycemic level in the blood which continued for about 2 months.

Swelling-controlled drug delivery copolymer gels were newly synthesized by introducing thermo- and pH-responsive methacryloyl-glycine (MA-Gly) or pH-responsive methacrylic acid (MA-Ac) for comparison with thermoresponsive acryloyl-L-proline ethyl ester (A-ProOEt). A homopolymer gel of A-ProOEt was kept at degrees of swelling that were less than 0.5 at a pH from 2.5 to 7.5 at 37 degrees C. The thresholds of swelling for copolymer gels consisting of A-ProOEt/MA-Gly and A-ProOEt/MA-Ac with a composition of 40/60 mol% were found to be pH 3.0 and pH 5.5, respectively, in buffer solutions at 37 degrees C. The diffusion characteristics of 2-(3-benzoylphenyl)propionic acid (ketoprofen) from such copolymer gels was evaluated in buffer solutions at pH's more than 5.5, and it was found that A-ProOEt/MA-Gly gel possesses a case II transport mechanism that is completely linear time dependent in both the amount diffused and the penetrating swelling front position. On the other hand, A-ProOEt/MA-Ac gel exhibited a non-Fickian (or anomalous) diffusion behavior under the same conditions.

A new nonnatural amino acid 3-[2-cyano-4-(dimethylamino)phenyl]alanine (CDAPA) is virtually nonfluorescent in water but shows significant enhancement of fluorescence intensity and lifetime when the...