FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3046603383> ?p ?o ?g. }

• W3046603383 endingPage "19833" @default.
• W3046603383 startingPage "19827" @default.
• W3046603383 abstract "Covalent cross-linking of biomolecules can be useful in pursuit of tissue targeting or dual targeting of two receptors on cell surfaces for avidity effects. Long linkers (>10 kDa) can be advantageous for such purposes, and poly(ethylene glycol) (PEG) linkers are most commonly used due to the high aqueous solubility of PEG and its relative inertness toward biological targets. However, PEG is non-biodegradable, and available PEG linkers longer than 5 kDa are heterogeneous (polydisperse), which means that conjugates based on such materials will be mixtures. We describe here recombinant linkers of distinct lengths, which can be expressed in yeast, which are polar, and which carry orthogonal reactivity at each end of the linker, thus allowing chemoselective cross-linking of proteins. A conjugate between insulin and either of the two trypsin inhibitor peptides/proteins exemplifies the technology, using a GQAP-based linker of molecular weight of 17 848, having one amine at the N-terminal, and one Cys, at the C-terminal. Notably, yeast-based expression systems typically give products with mixed disulfides when expressing proteins that are equipped with one unpaired Cys, namely, mixed disulfides with glutathione, free Cys amino acid, and/or a protein homodimer. To obtain a homogeneous linker, we worked out conditions for transforming the linker with mixed disulfides into a linker with a homogeneous disulfide, using excess 4-mercaptophenylacetic acid. Subsequently, the N-terminal amine of the linker was transformed into an azide, and the C-terminal Cys disulfide was reduced to a free thiol and reacted with halo-acetyl insulin. The N-terminal azide was finally conjugated to either of the two types of alkyne-containing trypsin inhibitor peptides/proteins. This reaction sequence allowed the cross-linked proteins to carry internal disulfides, as no reduction step was needed after protein conjugations. The insulin–trypsin inhibitor conjugates were shown to be stabilized toward enzymatic digestions and to have partially retained binding to the insulin receptor." @default.
• W3046603383 created "2020-08-07" @default.
• W3046603383 creator A5005754454 @default.
• W3046603383 creator A5013888878 @default.
• W3046603383 creator A5017852690 @default.
• W3046603383 creator A5030319348 @default.
• W3046603383 creator A5040776533 @default.
• W3046603383 creator A5061239123 @default.
• W3046603383 creator A5064053513 @default.
• W3046603383 creator A5085997583 @default.
• W3046603383 date "2020-07-31" @default.
• W3046603383 modified "2023-10-18" @default.
• W3046603383 title "Dually Reactive Long Recombinant Linkers for Bioconjugations as an Alternative to PEG" @default.
• W3046603383 cites W1884460322 @default.
• W3046603383 cites W1968652549 @default.
• W3046603383 cites W1971923734 @default.
• W3046603383 cites W1973206837 @default.
• W3046603383 cites W1978766165 @default.
• W3046603383 cites W1985426883 @default.
• W3046603383 cites W1995203966 @default.
• W3046603383 cites W2021320094 @default.
• W3046603383 cites W2077498510 @default.
• W3046603383 cites W2081643248 @default.
• W3046603383 cites W2082276184 @default.
• W3046603383 cites W2127986010 @default.
• W3046603383 cites W2128002420 @default.
• W3046603383 cites W2128950607 @default.
• W3046603383 cites W2146029618 @default.
• W3046603383 cites W2158901125 @default.
• W3046603383 cites W2165053262 @default.
• W3046603383 cites W2166171010 @default.
• W3046603383 cites W2198646935 @default.
• W3046603383 cites W2236678633 @default.
• W3046603383 cites W2291150896 @default.
• W3046603383 cites W2307168934 @default.
• W3046603383 cites W2316569370 @default.
• W3046603383 cites W2618254365 @default.
• W3046603383 cites W2786057985 @default.
• W3046603383 cites W2884662629 @default.
• W3046603383 doi "https://doi.org/10.1021/acsomega.0c02712" @default.
• W3046603383 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7424725" @default.
• W3046603383 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32803078" @default.
• W3046603383 hasPublicationYear "2020" @default.
• W3046603383 type Work @default.
• W3046603383 sameAs 3046603383 @default.
• W3046603383 citedByCount "4" @default.
• W3046603383 countsByYear W30466033832020 @default.
• W3046603383 countsByYear W30466033832021 @default.
• W3046603383 countsByYear W30466033832022 @default.
• W3046603383 countsByYear W30466033832023 @default.
• W3046603383 crossrefType "journal-article" @default.
• W3046603383 hasAuthorship W3046603383A5005754454 @default.
• W3046603383 hasAuthorship W3046603383A5013888878 @default.
• W3046603383 hasAuthorship W3046603383A5017852690 @default.
• W3046603383 hasAuthorship W3046603383A5030319348 @default.
• W3046603383 hasAuthorship W3046603383A5040776533 @default.
• W3046603383 hasAuthorship W3046603383A5061239123 @default.
• W3046603383 hasAuthorship W3046603383A5064053513 @default.
• W3046603383 hasAuthorship W3046603383A5085997583 @default.
• W3046603383 hasBestOaLocation W30466033831 @default.
• W3046603383 hasConcept C10138342 @default.
• W3046603383 hasConcept C111919701 @default.
• W3046603383 hasConcept C131779359 @default.
• W3046603383 hasConcept C134306372 @default.
• W3046603383 hasConcept C162324750 @default.
• W3046603383 hasConcept C178790620 @default.
• W3046603383 hasConcept C180577832 @default.
• W3046603383 hasConcept C181199279 @default.
• W3046603383 hasConcept C185592680 @default.
• W3046603383 hasConcept C197336794 @default.
• W3046603383 hasConcept C21951064 @default.
• W3046603383 hasConcept C2776964284 @default.
• W3046603383 hasConcept C2777516009 @default.
• W3046603383 hasConcept C2779149719 @default.
• W3046603383 hasConcept C2779201268 @default.
• W3046603383 hasConcept C2780340462 @default.
• W3046603383 hasConcept C2780557392 @default.
• W3046603383 hasConcept C2780997848 @default.
• W3046603383 hasConcept C33923547 @default.
• W3046603383 hasConcept C41008148 @default.
• W3046603383 hasConcept C49853544 @default.
• W3046603383 hasConcept C515207424 @default.
• W3046603383 hasConcept C54400483 @default.
• W3046603383 hasConcept C55493867 @default.
• W3046603383 hasConcept C71240020 @default.
• W3046603383 hasConceptScore W3046603383C10138342 @default.
• W3046603383 hasConceptScore W3046603383C111919701 @default.
• W3046603383 hasConceptScore W3046603383C131779359 @default.
• W3046603383 hasConceptScore W3046603383C134306372 @default.
• W3046603383 hasConceptScore W3046603383C162324750 @default.
• W3046603383 hasConceptScore W3046603383C178790620 @default.
• W3046603383 hasConceptScore W3046603383C180577832 @default.
• W3046603383 hasConceptScore W3046603383C181199279 @default.
• W3046603383 hasConceptScore W3046603383C185592680 @default.
• W3046603383 hasConceptScore W3046603383C197336794 @default.
• W3046603383 hasConceptScore W3046603383C21951064 @default.
• W3046603383 hasConceptScore W3046603383C2776964284 @default.
• W3046603383 hasConceptScore W3046603383C2777516009 @default.

• next