FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2974241521> ?p ?o ?g. }

• W2974241521 endingPage "109432" @default.
• W2974241521 startingPage "109432" @default.
• W2974241521 abstract "The potential anticancer activity of arginine deiminase (ADI) via deimination of l-arginine into citrulline has been extensively verified against various arginine-auxotrophic tumors, however, the higher antigenicity, structural instability and in vivo proteolysis are the major challenges that limit this enzyme from further clinical implementation. Since, this clinically applied enzyme was derived from Mycobacterium spp, thus, searching for ADI from eukaryotic microbes especially thermophilic fungi could have a novel biochemical, conformational and catalytic properties. Aspergillus nidulans ADI was purified with 5.3 folds, with molecular subunit structure 48 kDa and entire molecular mass 120 kDa, ensuring its homotrimeric identity. The peptide fingerprinting analysis revealing the domain Glu95-Gly96-Gly97 as the conserved active site of A. nidulans ADI, with higher proximity to Mycobacterium ADI clade IV. In an endeavor to fortify the structural stability and anticancer activity of A. nidulans ADI, the enzyme was chemically modified with dextran. The optimal activity of Dextran-ADI conjugates was determined at 0.08:20 M ratio of ADI: Dextran, with an overall increase to ADI molecular subunit mass to ˜100 kDa. ADI was conjugated with dextran via the ε-amino groups interaction of surface lysine residues of ADI. The resistance of Dextran-ADI conjugate to proteolysis had been increased by 2.5 folds to proteinase K and trypsin, suggesting the shielding of >50% of ADI surface proteolytic recognition sites. The native and Dextran-ADI conjugates have the same optimum reaction temperature (37 °C), reaction pH and pH stability (7.0-8.0) with dependency on K+ ions as a cofactor. Dextran-ADI conjugates exhibited a higher thermal stability by ˜ 2 folds for all the tested temperatures, ensuring the acquired structural and catalytic stability upon dextran conjugation. Dextran conjugation slightly protect the reactive amino and thiols groups of surface amino acids of ADI from amino acids suicide inhibitors. The affinity of ADI was increased by 5.3 folds to free L-arginine with a dramatic reduction in citrullination of peptidylarginine residues upon dextran conjugation. The anticancer activity of ADI to breast (MCF-7), liver (HepG-2) and colon (HCT8, HT29, DLD1 and LS174 T) cancer cell lines was increased by 1.7 folds with dextran conjugation in vitro. Pharmacokinetically, the half-life time of ADI was increased by 1.7 folds upon dextran conjugation, in vivo. From the biochemical and hematological parameters, ADIs had no signs of toxicity to the experimental animals. In addition to the dramatic reduction of L-arginine in serum, citrulline level was increased by 2.5 folds upon dextran conjugation of ADI. This is first report exploring thermostable ADI from thermophilic A. nidulans with robust structural stability, catalytic efficiency and proteolytic resistance." @default.
• W2974241521 created "2019-09-26" @default.
• W2974241521 creator A5023054541 @default.
• W2974241521 creator A5038272931 @default.
• W2974241521 creator A5041601133 @default.
• W2974241521 creator A5046916385 @default.
• W2974241521 creator A5068395471 @default.
• W2974241521 creator A5081381795 @default.
• W2974241521 date "2019-12-01" @default.
• W2974241521 modified "2023-10-06" @default.
• W2974241521 title "Aspergillus nidulans thermostable arginine deiminase-Dextran conjugates with enhanced molecular stability, proteolytic resistance, pharmacokinetic properties and anticancer activity" @default.
• W2974241521 cites W1547929361 @default.
• W2974241521 cites W1748154919 @default.
• W2974241521 cites W1757091502 @default.
• W2974241521 cites W1931048554 @default.
• W2974241521 cites W1943338444 @default.
• W2974241521 cites W1965551666 @default.
• W2974241521 cites W1967434609 @default.
• W2974241521 cites W1969088808 @default.
• W2974241521 cites W1983116683 @default.
• W2974241521 cites W1990332976 @default.
• W2974241521 cites W1990565169 @default.
• W2974241521 cites W1991366673 @default.
• W2974241521 cites W1998890104 @default.
• W2974241521 cites W2000472204 @default.
• W2974241521 cites W2010091762 @default.
• W2974241521 cites W2013206354 @default.
• W2974241521 cites W2014107195 @default.
• W2974241521 cites W2017212166 @default.
• W2974241521 cites W2028276286 @default.
• W2974241521 cites W2049066732 @default.
• W2974241521 cites W2052700765 @default.
• W2974241521 cites W2060481873 @default.
• W2974241521 cites W2060793088 @default.
• W2974241521 cites W2067233533 @default.
• W2974241521 cites W2071146934 @default.
• W2974241521 cites W2071328068 @default.
• W2974241521 cites W2072888427 @default.
• W2974241521 cites W2077637394 @default.
• W2974241521 cites W2077806459 @default.
• W2974241521 cites W2080915191 @default.
• W2974241521 cites W2087298783 @default.
• W2974241521 cites W2106712645 @default.
• W2974241521 cites W2110195508 @default.
• W2974241521 cites W2119785831 @default.
• W2974241521 cites W2122949433 @default.
• W2974241521 cites W2123218404 @default.
• W2974241521 cites W2145462268 @default.
• W2974241521 cites W2147998910 @default.
• W2974241521 cites W2157230119 @default.
• W2974241521 cites W2166051826 @default.
• W2974241521 cites W2269208301 @default.
• W2974241521 cites W2274550965 @default.
• W2974241521 cites W2319931815 @default.
• W2974241521 cites W2540831465 @default.
• W2974241521 cites W2580667306 @default.
• W2974241521 cites W2793456104 @default.
• W2974241521 cites W2886868067 @default.
• W2974241521 cites W2912294793 @default.
• W2974241521 cites W4241947376 @default.
• W2974241521 cites W4293247451 @default.
• W2974241521 doi "https://doi.org/10.1016/j.enzmictec.2019.109432" @default.
• W2974241521 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31615671" @default.
• W2974241521 hasPublicationYear "2019" @default.
• W2974241521 type Work @default.
• W2974241521 sameAs 2974241521 @default.
• W2974241521 citedByCount "33" @default.
• W2974241521 countsByYear W29742415212020 @default.
• W2974241521 countsByYear W29742415212021 @default.
• W2974241521 countsByYear W29742415212022 @default.
• W2974241521 countsByYear W29742415212023 @default.
• W2974241521 crossrefType "journal-article" @default.
• W2974241521 hasAuthorship W2974241521A5023054541 @default.
• W2974241521 hasAuthorship W2974241521A5038272931 @default.
• W2974241521 hasAuthorship W2974241521A5041601133 @default.
• W2974241521 hasAuthorship W2974241521A5046916385 @default.
• W2974241521 hasAuthorship W2974241521A5068395471 @default.
• W2974241521 hasAuthorship W2974241521A5081381795 @default.
• W2974241521 hasConcept C104317684 @default.
• W2974241521 hasConcept C143065580 @default.
• W2974241521 hasConcept C181199279 @default.
• W2974241521 hasConcept C185592680 @default.
• W2974241521 hasConcept C2776923806 @default.
• W2974241521 hasConcept C2777186326 @default.
• W2974241521 hasConcept C2777339698 @default.
• W2974241521 hasConcept C2777468819 @default.
• W2974241521 hasConcept C2781307694 @default.
• W2974241521 hasConcept C515207424 @default.
• W2974241521 hasConcept C55493867 @default.
• W2974241521 hasConcept C58121356 @default.
• W2974241521 hasConceptScore W2974241521C104317684 @default.
• W2974241521 hasConceptScore W2974241521C143065580 @default.
• W2974241521 hasConceptScore W2974241521C181199279 @default.
• W2974241521 hasConceptScore W2974241521C185592680 @default.
• W2974241521 hasConceptScore W2974241521C2776923806 @default.
• W2974241521 hasConceptScore W2974241521C2777186326 @default.
• W2974241521 hasConceptScore W2974241521C2777339698 @default.
• W2974241521 hasConceptScore W2974241521C2777468819 @default.

• next