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Coiled coil peptides as universal linkers for the attachment of recombinant proteins to polymer therapeutics
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SYSNO ASEP 0364976 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Coiled coil peptides as universal linkers for the attachment of recombinant proteins to polymer therapeutics Author(s) Pechar, Michal (UMCH-V) RID, ORCID
Pola, Robert (UMCH-V) RID, ORCID
Laga, Richard (UMCH-V) RID, ORCID
Ulbrich, Karel (UMCH-V) RID
Bednárová, Lucie (UOCHB-X) RID, ORCID
Maloň, Petr (UOCHB-X)
Sieglová, Irena (UMG-J)
Král, Vlastimil (UMG-J) RID
Fábry, Milan (UMG-J) RID
Vaněk, O. (CZ)Source Title Biomacromolecules. - : American Chemical Society - ISSN 1525-7797
Roč. 12, č. 10 (2011), s. 3645-3655Number of pages 11 s. Language eng - English Country US - United States Keywords coiled coil ; polymer therapeutics ; drug targeting Subject RIV CC - Organic Chemistry R&D Projects GA203/08/0543 GA ČR - Czech Science Foundation (CSF) 1M0505 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) CEZ AV0Z40500505 - UMCH-V (2005-2011) AV0Z40550506 - UOCHB-X (2005-2011) AV0Z50520514 - UMG-J (2005-2011) UT WOS 000295602600032 DOI 10.1021/bm200897b Annotation We prepared peptides containing four repeats of the sequences VAALEKE (peptide E) or VAALKEK (peptide K). While the peptides alone adopt in aqueous solutions a random coil conformation, their equimolar mixture forms heterodimeric coiled coils as confirmed by CD spectroscopy. A terminal azide group enabled conjugation of the peptide with a synthetic drug carrier based on the N-(2-hydroxypropyl)methacrylamide copolymer containing propargyl groups using “click” chemistry. When incorporated into the polymer drug carrier, peptide E formed a stable noncovalent complex with peptide K belonging to a recombinant single-chain fragment (scFv) of the M75 antibody. The complex mediated a noncovalent linkage between the polymer drug carrier and the protein. The antigen binding affinity of the polymer−scFv complex was confirmed by ELISA. This approach offers a well-defined, specific, and nondestructive universal method for the preparation of protein-targeted polymer drug carriers. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2012
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