Premium
On‐Resin Synthesis of an Acylated and Fluorescence‐Labeled Cyclic Integrin Ligand for Modification of Poly(lactic‐co‐glycolic acid)
Author(s) -
Hassert Rayk,
Hoffmeister PeterGeorg,
Pagel Mareen,
Hacker Michael,
SchulzSiegmund Michaela,
BeckSickinger Annette G.
Publication year - 2012
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201200290
Subject(s) - chemistry , plga , lipopeptide , integrin , glycolic acid , cyclic peptide , combinatorial chemistry , peptide , click chemistry , biophysics , biocompatibility , drug delivery , receptor , biochemistry , lactic acid , in vitro , organic chemistry , bacteria , biology , genetics
Cyclic Arg‐Gly‐Asp (RGD) peptides show remarkable affinity and specificity to integrin receptors and mediate important physiological effects in tumor angiogenesis. Additionally, they are one of the keyplayers in improving the biocompatibility of biomaterials. The fully biodegradable polymer poly(lactic‐co‐glycolic acid) (PLGA) is frequently used for biomedical implants and can be applied as nanoparticles for drug delivery. The aim of this work was the generation of a lipidated c[RGDfK] peptide including a second functionality for coating of hydrophobic PLGA. Therefore, we established a general and straightforward strategy for the introduction of two different modifications into the same c[RGDfK] peptide. This allowed the generation of a palmitoylated integrin‐binding lipopeptide that shows high affinity to PLGA. Additionally, we coupled 5(6)‐carboxyfluorescein to the second site for modification to enable sensitive quantification of the immobilized lipopeptide on PLGA. In conclusion, we present a synthesis protocol that enables the preparation of c[RGDfK] lipopeptides with a strong affinity to PLGA and an additional site for modifications. This will provide the opportunity to introduce a variety of effector molecules site‐specifically to the c[RGDfK] lipopeptide, which will enable the introduction of multifunctionality into c[RGDfK]‐coated PLGA devices or nanoparticles.