title: On-resin synthesis of an acylated and fluorescence-labeled cyclic integrin ligand for modification of poly(lactic-co-glycolic acid).
abstract: 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.
authors.affiliation: Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Universität Leipzig, Brüderstrasse 34, D-04103 Leipzig, Germany.
authors.forename: Rayk
authors.initials: R
authors.lastname: Hassert
authors.forename: Peter-Georg
authors.initials: PG
authors.lastname: Hoffmeister
authors.forename: Mareen
authors.initials: M
authors.lastname: Pagel
authors.forename: Michael
authors.initials: M
authors.lastname: Hacker
authors.forename: Michaela
authors.initials: M
authors.lastname: Schulz-Siegmund
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
mesh_terms: D000215:Acylation; D003500:Cyclization; D005452:Fluoresceins / Q000138:chemical synthesis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D016023:Integrins / Q000378:metabolism; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D016023:Integrins; D008024:Ligands; D008055:Lipids; D009842:Oligopeptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C024098:6-carboxyfluorescein; D019344:Lactic Acid; C047981:arginyl-glycyl-aspartic acid