Abstract:
:Polymer therapeutics, including polymeric drugs and polymer-protein conjugates, are clinically established as first-generation nanomedicines. Knowing that the coiled-coil peptide motif is fundamentally important in the regulation of many cellular and pathological processes, the aim of these studies was to examine the feasibility of designing polymer conjugates containing the coiled-coil motif as a putative therapeutic "molecular switch". To establish proof of concept, we prepared a mPEG-FosW(C) conjugate by reacting mPEG-maleimide (M(w) 5522 g mol(-1), M(w)/M(n) 1.1) with a FosW peptide synthesized to contain a terminal cysteine residue (FosW(C)). Its ability to form a stable coil-coil heterodimer with the target c-Jun sequence of the oncogenic AP-1 transcription factor was investigated using 2D (15)N-HSQC NMR together with a recombinantly prepared (15)N-labeled c-Jun peptide ([(15)N]r-c-Jun). Observation that heterodimerization was achieved and that the polymer did not sterically disadvantage hybridization suggests an important future for this new family of polymer therapeutics.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Deacon SP,Apostolovic B,Carbajo RJ,Schott AK,Beck K,Vicent MJ,Pineda-Lucena A,Klok HA,Duncan Rdoi
10.1021/bm100843esubject
Has Abstractpub_date
2011-01-10 00:00:00pages
19-27issue
1eissn
1525-7797issn
1526-4602journal_volume
12pub_type
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