FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3195035861> ?p ?o ?g. }

• W3195035861 endingPage "1769" @default.
• W3195035861 startingPage "1757" @default.
• W3195035861 abstract "Cysteine-rich knob domains found in the ultralong complementarity determining regions of a subset of bovine antibodies are capable of functioning autonomously as 3–6 kDa peptides. While they can be expressed recombinantly in cellular systems, in this paper we show that knob domains are also readily amenable to a chemical synthesis, with a co-crystal structure of a chemically synthesized knob domain in complex with an antigen showing structural equivalence to the biological product. For drug discovery, following the immunization of cattle, knob domain peptides can be synthesized directly from antibody sequence data, combining the power and diversity of the bovine immune repertoire with the ability to rapidly incorporate nonbiological modifications. We demonstrate that, through rational design with non-natural amino acids, a paratope diversity can be massively expanded, in this case improving the efficacy of an allosteric peptide. As a potential route to further improve stability, we also performed head-to-tail cyclizations, exploiting the proximity of the N and C termini to synthesize functional, fully cyclic antibody fragments. Lastly, we highlight the stability of knob domains in plasma and, through pharmacokinetic studies, use palmitoylation as a route to extend the plasma half-life of knob domains in vivo. This study presents an antibody-derived medicinal chemistry platform, with protocols for solid-phase synthesis of knob domains, together with the characterization of their molecular structures, in vitro pharmacology, and pharmacokinetics." @default.
• W3195035861 created "2021-08-30" @default.
• W3195035861 creator A5002314973 @default.
• W3195035861 creator A5007386430 @default.
• W3195035861 creator A5008133089 @default.
• W3195035861 creator A5022515446 @default.
• W3195035861 creator A5025921355 @default.
• W3195035861 creator A5026032024 @default.
• W3195035861 creator A5028663303 @default.
• W3195035861 creator A5031031508 @default.
• W3195035861 creator A5031581431 @default.
• W3195035861 creator A5032087487 @default.
• W3195035861 creator A5035813084 @default.
• W3195035861 creator A5048832652 @default.
• W3195035861 creator A5061961032 @default.
• W3195035861 creator A5061987995 @default.
• W3195035861 creator A5064350904 @default.
• W3195035861 creator A5069413856 @default.
• W3195035861 creator A5070141146 @default.
• W3195035861 creator A5074658052 @default.
• W3195035861 creator A5078103824 @default.
• W3195035861 creator A5079932070 @default.
• W3195035861 creator A5083087899 @default.
• W3195035861 creator A5091080514 @default.
• W3195035861 date "2021-08-18" @default.
• W3195035861 modified "2023-10-02" @default.
• W3195035861 title "The Chemical Synthesis of Knob Domain Antibody Fragments" @default.
• W3195035861 cites W1491301840 @default.
• W3195035861 cites W1497549653 @default.
• W3195035861 cites W1964538987 @default.
• W3195035861 cites W1977459493 @default.
• W3195035861 cites W2033079214 @default.
• W3195035861 cites W2034380547 @default.
• W3195035861 cites W2035503835 @default.
• W3195035861 cites W2084336971 @default.
• W3195035861 cites W2089409411 @default.
• W3195035861 cites W2095553811 @default.
• W3195035861 cites W2104630130 @default.
• W3195035861 cites W2106686914 @default.
• W3195035861 cites W2144234477 @default.
• W3195035861 cites W2317417725 @default.
• W3195035861 cites W2482075725 @default.
• W3195035861 cites W2737872184 @default.
• W3195035861 cites W2752563387 @default.
• W3195035861 cites W2769533173 @default.
• W3195035861 cites W2789839027 @default.
• W3195035861 cites W2884846105 @default.
• W3195035861 cites W2889540205 @default.
• W3195035861 cites W2942650326 @default.
• W3195035861 cites W2947399142 @default.
• W3195035861 cites W2980135126 @default.
• W3195035861 cites W3025775216 @default.
• W3195035861 cites W3083338080 @default.
• W3195035861 cites W3087613416 @default.
• W3195035861 cites W3091911488 @default.
• W3195035861 cites W3129134816 @default.
• W3195035861 cites W3157819115 @default.
• W3195035861 doi "https://doi.org/10.1021/acschembio.1c00472" @default.
• W3195035861 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34406751" @default.
• W3195035861 hasPublicationYear "2021" @default.
• W3195035861 type Work @default.
• W3195035861 sameAs 3195035861 @default.
• W3195035861 citedByCount "9" @default.
• W3195035861 countsByYear W31950358612021 @default.
• W3195035861 countsByYear W31950358612022 @default.
• W3195035861 countsByYear W31950358612023 @default.
• W3195035861 crossrefType "journal-article" @default.
• W3195035861 hasAuthorship W3195035861A5002314973 @default.
• W3195035861 hasAuthorship W3195035861A5007386430 @default.
• W3195035861 hasAuthorship W3195035861A5008133089 @default.
• W3195035861 hasAuthorship W3195035861A5022515446 @default.
• W3195035861 hasAuthorship W3195035861A5025921355 @default.
• W3195035861 hasAuthorship W3195035861A5026032024 @default.
• W3195035861 hasAuthorship W3195035861A5028663303 @default.
• W3195035861 hasAuthorship W3195035861A5031031508 @default.
• W3195035861 hasAuthorship W3195035861A5031581431 @default.
• W3195035861 hasAuthorship W3195035861A5032087487 @default.
• W3195035861 hasAuthorship W3195035861A5035813084 @default.
• W3195035861 hasAuthorship W3195035861A5048832652 @default.
• W3195035861 hasAuthorship W3195035861A5061961032 @default.
• W3195035861 hasAuthorship W3195035861A5061987995 @default.
• W3195035861 hasAuthorship W3195035861A5064350904 @default.
• W3195035861 hasAuthorship W3195035861A5069413856 @default.
• W3195035861 hasAuthorship W3195035861A5070141146 @default.
• W3195035861 hasAuthorship W3195035861A5074658052 @default.
• W3195035861 hasAuthorship W3195035861A5078103824 @default.
• W3195035861 hasAuthorship W3195035861A5079932070 @default.
• W3195035861 hasAuthorship W3195035861A5083087899 @default.
• W3195035861 hasAuthorship W3195035861A5091080514 @default.
• W3195035861 hasBestOaLocation W31950358611 @default.
• W3195035861 hasConcept C114373084 @default.
• W3195035861 hasConcept C159654299 @default.
• W3195035861 hasConcept C166342909 @default.
• W3195035861 hasConcept C170493617 @default.
• W3195035861 hasConcept C181199279 @default.
• W3195035861 hasConcept C185592680 @default.
• W3195035861 hasConcept C195616568 @default.
• W3195035861 hasConcept C202751555 @default.

• next