Coiled coil peptides as universal linkers for the attachment of recombinant proteins to polymer therapeutics

0364976 - ÚMCH 2012 RIV US eng J - Článek v odborném periodiku
Pechar, Michal - Pola, Robert - Laga, Richard - Ulbrich, Karel - Bednárová, Lucie - Maloň, Petr - Sieglová, Irena - Král, Vlastimil - Fábry, Milan - Vaněk, O.
Coiled coil peptides as universal linkers for the attachment of recombinant proteins to polymer therapeutics.
Biomacromolecules. Roč. 12, č. 10 (2011), s. 3645-3655. ISSN 1525-7797. E-ISSN 1526-4602
Grant CEP: GA ČR GA203/08/0543; GA MŠMT 1M0505
Výzkumný záměr: CEZ:AV0Z40500505; CEZ:AV0Z40550506; CEZ:AV0Z50520514
Klíčová slova: coiled coil * polymer therapeutics * drug targeting
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 5.479, rok: 2011

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.
Trvalý link: http://hdl.handle.net/11104/0006572