Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0267964 (PAA)
 2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PP10 was isolated from aqueous extracts of human term placentae by fractionating the proteins with rivanol and ammonium sulfate, by gelfiltration on Sephadex G-150 and by use of immunoadsorbents. PP10 apparently is a protein specific for the placenta; it could not be detected in extracts from other human tissues. From one human term placenta an average amount of 20 mg PP10 can be extracted. In sera from pregnant women PP10 is usually present only in trace amounts (less than 0.1 mg/100 ml). PP10 has the electrophoretic mobility of an alpha1-globulin and an isoelectric point of 5.1. The purified protein sediments with 3.8 S. PP10 was found to have a molecular weight of 48,000 as determined by ultracentrifugation and a molecular weight of 65,000 as determined by SDS-PAA gel electrophoresis. PP10 is a glycoprotein containing 6.65% carbohydrates (hexoses 4.8%, hexosamines 1.2%, fucose 0.05%, sialic acid 0.6%). The amino acid composition of PP10 has been determined, too; the most abundant amino acids in this protein are glutamic acid, aspartic acid, leucine and alanine.
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PMID:[Isolation and characterization of a new placenta specific protein (PP10) (author's transl)]. 48 20

The plasma and tissue distribution of doxorubicin-poly-L-aspartic acid (DX-PAA) and doxorubicin (DX) at equitoxic doses have been studied by a fluorescence assay in tumor bearing mice following administration of a single i.v. bolus injection. A relatively short distribution phase followed by a slow elimination phase characterized the DX-PAA plasma disappearence: at 48 hr after the treatment the conjugate was still detected in plasma. The plasma under the concentration vs. time curve (AUC) of drug equivalents following free DX administration resulted 2.6 times higher than the plasma AUC of free equivalents produced by DX-PAA treatment. In lung, liver and spleen the DX-PAA was accumulated in high concentrations. Low amount of DX equivalents were found in the heart following the conjugate administration: after 2 hr only traces of free anthracycline equivalents were detectable. On the contrary, drug equivalents following free DX treatment remained evaluable in the heart up to 24 hr from the drug administration. No significative differences were observed in the tumor AUC of free DX equivalents produced by free or polymer-linked DX. These data suggest that DX-PAA might act as a depot system slowly releasing the cytotoxic agent. Furthermore the observed accumulation of the conjugate and free DX equivalents in the lung and in the liver suggest a possible therapeutic advantages of DX-PAA in tumors with potential metastasis in these organs.
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PMID:Comparative distribution of free doxorubicin and poly-L-aspartic acid linked doxorubicin in MS-2 sarcoma bearing mice. 377 1

The synthetic polypeptide, poly-L-aspartic acid (PAA, mol. wt = 20,000) has been used as a macromolecular carrier for doxorubicin. The drug may be released in vivo through hydrolysis of the ester linkage formed between the carboxyl groups of the polymer and the drug side chain. PAA has been found to be a suitable carrier since it is a soluble, biodegradable, multivalent and nontoxic polymer. The toxicity and the therapeutic efficacy of free and polymer-linked doxorubicin have been evaluated in normal and tumour-bearing mice, using a variety of experimental tumour systems. In studies on single and multiple drug administration, the results indicated that the polymeric derivative of doxorubicin had approximately 3-fold lower toxicity than did free drug. In addition, the severity of specific toxic effects, including cardio- and vesicant toxicity, were appreciably reduced following conjugation to PAA. The doxorubicin-PAA conjugate gave similar or rather greater therapeutic effects than free drug at less toxic doses. This effect, more evident in the highly sensitive tumours, suggests an improvement of the therapeutic index of the polymer-linked drug.
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PMID:Poly-L-aspartic acid as a carrier for doxorubicin: a comparative in vivo study of free and polymer-bound drug. 407 38

We tested a newly developed ultrasound contrast agent (LK565) from poly-aspartic acid (PAA; particle size 3 microns; particle content: air) in 15 healthy male probands (20-38 years) in doses of 10, 30 and 100 mg intravenously. One day and immediately before the study a routine laboratory test, an ECG and an EEG were performed. The EEG was continued through the complete time period that the ultrasound contrast lasted, i.e., up to one hour after the injection. All probands were followed clinically for 24 hours when the routine laboratory and the ECG were repeated. All subjects tolerated the contrast agent well. There were no changes in either the EEG or in the ECGs performed throughout the study. There were no significant laboratory changes except for a small and transient increase in the neutrophil count in five probands receiving the highest dose. All injections with 10 mg led to a significant improvement in the color Doppler signal. All injections with 30 and 100 mg led to a very strong echo contrast lasting for 5 to 12 minutes in the harmonic B-mode. Using the latter, fragments of intramyocardial coronaries could be visualized. The tested ultrasound polymer contrast agent was safe, well tolerated and efficient in this acute study.
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PMID:[Safety and efficacy of LK565--a new polymer ultrasound contrast medium]. 1148 77

Microbial degradation of thermally synthesized poly(aspartic acid) (PAA) was investigated. A PAA-P1 sample (Mn, 7500; Mw, 20,000; number of branched units/100 monomer units, 3.1) was completely degraded in natural river water within 15 days at 25 degrees C. A new PAA-degrading bacterium (strain KP-2: JCM10638) was isolated together with Sphingomonas sp. KT-1 (JCM10459) from river water, and identified as a member of Pedobacter. A Pedobacter isolate was capable of degrading high-molecular-weight PAA polymers of 5000 to 150,000, and a small amount of low-molecular-weight products of 250 to 5000 was accumulated as residues during the growth of the isolate on PAA. In contrast, the other isolate Sphingomonas sp. KT-1 degraded only low-molecular-weight PAA below 5000. A mixed culturing of Pedobacter sp. KP-2 with Sphingomonas sp. KT-1 resulted in a complete degradation of PAA-P1 sample, but a small amount of low molecular weight components was accumulated during the degradation of highly branched PAA-P2 and PAA-P3 samples.
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PMID:Microbial degradation of poly(aspartic acid) by two isolated strains of Pedobacter sp. and Sphingomonas sp. 1171 94

Poly(aspartic acid) (PAA) hydrolase was purified from Sphingomonas sp. KT-1 (JCM10459). The purified hydrolase degraded thermally synthesized PAA to oligomers. The molecular mass of PAA hydrolase was 30 kDa and the isoelectric point was 8.9. The optimum values of pH and temperature for PAA degradation were 10.0 and 40 degrees C, respectively. The investigation of the effect of inhibitors for the PAA-degrading activities has revealed that the PAA hydrolase is a serine-type hydrolase. The structural analysis of PAA-degraded products using (1)H and (13)C nuclear magnetic resonances has indicated that the purified enzyme hydrolyzes selectively the beta-amide linkage connecting with beta-aspartic acid units in PAA.
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PMID:Purification and characterization of poly(aspartic acid) hydrolase from Sphingomonas sp. KT-1. 1177 87

Gene transfer vectors formed between the cationic polyamino acid, poly-(L)-omithine (PLO) and plasmid DNA (pDNA) have demonstrated superior transfection efficiency (up to x 10-fold) compared to equivalent polylysine-based systems in-vitro. The mechanism(s) underlying this observation remains to be elucidated. We previously reported no significant difference in colloidal particle size or zeta potential of polycation/pDNA complexes formed with poly-(L)-lysine (PLL), poly-(D)-lysine (PDL) or PLO. Here we report spectrofluorometric analysis indicating that PLO condenses pDNA at lower charge (+/-) ratios than PLL or PDL (cf. 0.8:1, 1.2:1 and 1.5:1). Moreover, PLO/pDNA complexes proved more stable to disruption by the polyanions, poly-(L)-aspartic acid (PAA) and heparin. There were no qualitative differences in the ability of the polycations to protect complexed pDNA from enzymatic degradation both in the presence and in the absence of polyanions. The superior transfection efficiency of PLO/pDNA complexes did not appear to be mediated by an increased cellular delivery of pDNA. The data suggests a greater affinity of PLO for pDNA as an important parameter for the observed superior in-vitro transfection efficiency.
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PMID:Polylysine and polyornithine gene transfer complexes: a study of complex stability and cellular uptake as a basis for their differential in-vitro transfection efficiency. 1199 81

Sphingomonas sp. KT-1 hydrolyzes poly(aspartic acid) (PAA) containing alpha- and beta-amide units and has at least two different types of PAA hydrolases. The PAA hydrolase-1 hydrolyzes selectively beta-beta amide units in PAA. Molecular cloning of PAA hydrolase-1 from Sphingomonas sp. KT-1 has been carried out to characterize its gene products. Genetic analysis shows that the deduced amino acid sequence of PAA hydrolase-1 has a similarity with those of the catalytic domain of poly(3-hydroxybutyric acid) (PHB) depolymerases from Alcaligenes faecalis AE122 and Pseudomonas lemoignei. Site-specific mutation analysis indicates that (176)Ser is a part of a strictly conserved pentapeptide sequence (Gly-Xaa-Ser-Xaa-Gly), which is the lipase box, and plays as an active residue.
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PMID:Genetic analysis and characterization of poly(aspartic acid) hydrolase-1 from Sphingomonas sp. KT-1. 1252 51

Poly(aspartic acid) (PAA) hydrolase-2 was purified from crude soluble cellular extracts of Sphingomonas sp. KT-1 (JCM10459) and characterized to elucidate the mechanism of alpha,beta-poly(d,l-aspartic acid) (tPAA) biodegradation. The molecular mass of PAA hydrolase-2 was 42 kDa, and the isoelectric point was 9.6. The optimum values of pH and temperature for the hydrolysis of alpha-di(l-aspartic acid) by PAA hydrolase-2 were 7.0 and 55 degrees C, respectively. The effect of inhibitors on the hydrolysis of alpha-di(l-aspartic acid) showed that the activity of PAA hydrolase-2 was significantly inhibited by EDTA. Thermally synthesized tPAA was hydrolyzed in the presence of two enzymes, PAA hydrolase-1 and PAA hydrolase-2, to generate aspartic acid. The PAA hydrolase-2 was capable of hydrolyzing alpha-poly(l-aspartic acid) of high molecular weights but had limited activity for tPAA. These results lead us to propose the following mechanism. First, PAA hydrolase-1 hydrolyzes tPAA to yield oligo(aspartic acid) via an endo-mode cleavage, and subsequently, PAA hydrolase-2 hydrolyzes the resultant oligo(aspartic acid) to yield aspartic acid. Analysis of hydrolyzed products from alpha- and beta-penta(l-aspartic acid) revealed that PAA hydrolase-2 catalyzed the exo-mode hydrolysis of alpha- and beta-penta (l-aspartic acid). The gene encoding PAA hydrolase-2 from Sphingomonas sp. KT-1 was cloned, and genetic analysis showed that the deduced amino acid sequence of PAA hydrolase-2 is similar to a putative peptidase, which belongs to the M20/M25/M40 family of proteins, from Caulobacter crescentus CB15.
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PMID:Biochemical and molecular characterization of poly(aspartic acid) hydrolase-2 from sphingomonas sp. KT-1. 1295 96

The organic-inorganic hybrid nanoparticles entrapping oligodeoxynucleotide (ODN) or siRNA were prepared through the self-associating phenomenon of the block copolymer, poly(ethylene glycol)-block-poly(aspartic acid) (PEG-PAA), with calcium phosphate. The nanoparticles have diameters in the range of several hundreds of nanometers depending on the PEG-PAA concentration and revealed excellent colloidal stability due to the steric repulsion effect of the PEG layer surrounding the calcium phosphate core. The loading capacities of ODN and siRNA were fairly high, reaching almost 100% under optimal conditions. The flowcytometric analysis and confocal microscopy observation indicated that the hybrid nanoparticles loaded with ODN were taken up by the cells through the endocytosis mechanism. Furthermore, the calcium phosphate core dissociates in the intracellular environment with appreciably lowered calcium ion concentration compared to the exterior, allowing the release of the incorporated ODN and siRNA in a controlled manner. Eventually, effective intracellular delivery and nuclear localization of these nucleic acid-based drugs were evidenced through the observation of laser confocal microscopy using FITC-labeled ODN. This smart ion-sensitive characteristic of hybrid nanoparticles was further demonstrated by the appreciable silencing of reporter gene expression by siRNA incorporated in the nanoparticles.
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PMID:Block copolymer-coated calcium phosphate nanoparticles sensing intracellular environment for oligodeoxynucleotide and siRNA delivery. 1519 61


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