FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200206529> ?p ?o ?g. }

• W4200206529 abstract "Human thymidine phosphorylase (HsTP) is an enzyme with important implications in the field of rare metabolic diseases. Defective mutations of HsTP lead to mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a disease with a high unmet medical need that is associated with severe neurological and gastrointestinal complications. Current efforts focus on the development of an enzyme replacement therapy (ERT) using the Escherichia coli ortholog (EcTP). However, bacterial enzymes are counter-indicated for human therapeutic applications because they are recognized as foreign by the human immune system, thereby eliciting adverse immune responses and raising significant safety and efficacy risks. Thus, it is critical to utilize the HsTP enzyme as starting scaffold for pre-clinical drug development, thus de-risking the safety concerns associated with the use of bacterial enzymes. However, HsTP expresses very poorly in E. coli, whereas its PEGylation, a crucial chemical modification for achieving long serum persistence of therapeutic enzymes, is highly inefficient and negatively affects its catalytic activity. Here we focused on the engineering of the recombinant expression profile of HsTP in E. coli cells, as well as on the optimization of its PEGylation efficiency aiming at the development of an alternative therapeutic approach for MNGIE. We show that phylogenetic and structural analysis of proteins can provide important insights for the rational design of N'-terminus-truncation constructs which exhibit significantly improved recombinant expression levels. In addition, we developed and implemented a criteria-driven rational surface engineering strategy for the substitution of arginine-to-lysine and lysine-to-arginine residues to achieve more efficient, homogeneous and reproducible PEGylation without negatively affecting the enzymatic catalytic activity upon PEGylation. Collectively, our proposed strategies provide an effective way to optimize enzyme PEGylation and E. coli recombinant expression and are likely applicable for other proteins and enzymes." @default.
• W4200206529 created "2021-12-31" @default.
• W4200206529 creator A5018903903 @default.
• W4200206529 creator A5019442979 @default.
• W4200206529 creator A5023742482 @default.
• W4200206529 creator A5044737140 @default.
• W4200206529 date "2021-12-17" @default.
• W4200206529 modified "2023-10-17" @default.
• W4200206529 title "Engineering of the Recombinant Expression and PEGylation Efficiency of the Therapeutic Enzyme Human Thymidine Phosphorylase" @default.
• W4200206529 cites W1587071366 @default.
• W4200206529 cites W1603423304 @default.
• W4200206529 cites W1839516892 @default.
• W4200206529 cites W1864152843 @default.
• W4200206529 cites W1877106271 @default.
• W4200206529 cites W1965673191 @default.
• W4200206529 cites W1965816300 @default.
• W4200206529 cites W1965918908 @default.
• W4200206529 cites W1968380675 @default.
• W4200206529 cites W1974384202 @default.
• W4200206529 cites W1985262278 @default.
• W4200206529 cites W1995786921 @default.
• W4200206529 cites W2011501000 @default.
• W4200206529 cites W2012297445 @default.
• W4200206529 cites W2013470743 @default.
• W4200206529 cites W2015167700 @default.
• W4200206529 cites W2022234371 @default.
• W4200206529 cites W2025445920 @default.
• W4200206529 cites W2026255963 @default.
• W4200206529 cites W2027081836 @default.
• W4200206529 cites W2035761729 @default.
• W4200206529 cites W2036407487 @default.
• W4200206529 cites W2041275298 @default.
• W4200206529 cites W2041983529 @default.
• W4200206529 cites W2047360542 @default.
• W4200206529 cites W2050142915 @default.
• W4200206529 cites W2051238123 @default.
• W4200206529 cites W2051768266 @default.
• W4200206529 cites W2052099119 @default.
• W4200206529 cites W2054339156 @default.
• W4200206529 cites W2055218751 @default.
• W4200206529 cites W2060421156 @default.
• W4200206529 cites W2063160140 @default.
• W4200206529 cites W2068433825 @default.
• W4200206529 cites W2072714570 @default.
• W4200206529 cites W2084213291 @default.
• W4200206529 cites W2087963139 @default.
• W4200206529 cites W2096918975 @default.
• W4200206529 cites W2112687126 @default.
• W4200206529 cites W2113550611 @default.
• W4200206529 cites W2113910663 @default.
• W4200206529 cites W2114767579 @default.
• W4200206529 cites W2115957530 @default.
• W4200206529 cites W2120067067 @default.
• W4200206529 cites W2123467717 @default.
• W4200206529 cites W2123863402 @default.
• W4200206529 cites W2138820253 @default.
• W4200206529 cites W2144773160 @default.
• W4200206529 cites W2148458061 @default.
• W4200206529 cites W2153226970 @default.
• W4200206529 cites W2155024437 @default.
• W4200206529 cites W2159420012 @default.
• W4200206529 cites W2162907832 @default.
• W4200206529 cites W2164407102 @default.
• W4200206529 cites W2178979771 @default.
• W4200206529 cites W2254121776 @default.
• W4200206529 cites W2267867298 @default.
• W4200206529 cites W2285775467 @default.
• W4200206529 cites W2305195196 @default.
• W4200206529 cites W2323775454 @default.
• W4200206529 cites W2346414002 @default.
• W4200206529 cites W2395549144 @default.
• W4200206529 cites W2409257097 @default.
• W4200206529 cites W2422586284 @default.
• W4200206529 cites W2476819346 @default.
• W4200206529 cites W2512641548 @default.
• W4200206529 cites W2515002494 @default.
• W4200206529 cites W2554956457 @default.
• W4200206529 cites W2581689098 @default.
• W4200206529 cites W2585555058 @default.
• W4200206529 cites W2614618572 @default.
• W4200206529 cites W2766089724 @default.
• W4200206529 cites W2781628145 @default.
• W4200206529 cites W2809695658 @default.
• W4200206529 cites W2883967352 @default.
• W4200206529 cites W2888053567 @default.
• W4200206529 cites W2897248901 @default.
• W4200206529 cites W2906421409 @default.
• W4200206529 cites W2907856991 @default.
• W4200206529 cites W2910937685 @default.
• W4200206529 cites W2911502841 @default.
• W4200206529 cites W2913592752 @default.
• W4200206529 cites W2944031322 @default.
• W4200206529 cites W2951694379 @default.
• W4200206529 cites W2952214797 @default.
• W4200206529 cites W2960982755 @default.
• W4200206529 cites W2963717756 @default.
• W4200206529 cites W2988015966 @default.
• W4200206529 cites W3001103362 @default.
• W4200206529 cites W3016216867 @default.
• W4200206529 cites W3109332997 @default.

• next