title: A Green Light-Triggerable RGD Peptide for Photocontrolled Targeted Drug Delivery: Synthesis and Photolysis Studies.
abstract: We describe for the first time the synthesis and photochemical properties of a coumarin-caged cyclic RGD peptide and demonstrate that uncaging can be efficiently performed with biologically compatible green light. This was accomplished by using a new dicyanocoumarin derivative (DEAdcCE) for the protection of the carboxyl function at the side chain of the aspartic acid residue, which was selected on the basis of Fmoc-tBu SPPS compatibility and photolysis efficiency. The shielding effect of a methyl group incorporated in the coumarin derivative near the ester bond linking both moieties in combination with the use of acidic additives such as HOBt or Oxyma during the basic Fmoc-removal treatment were found to be very effective for minimizing aspartimide-related side reactions. In addition, a conjugate between the dicyanocoumarin-caged cyclic RGD peptide and ruthenocene, which was selected as a metallodrug model cargo, has been synthesized and characterized. The fact that green-light triggered photoactivation can be efficiently performed both with the caged peptide and with its ruthenocenoyl bioconjugate reveals great potential for DEAdcCE-caged peptide sequences as selective drug carriers in the context of photocontrolled targeted anticancer strategies.
authors.affiliation: Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, IBUB, Universitat de Barcelona , E-08028 Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Gandioso
authors.affiliation: Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, IBUB, Universitat de Barcelona , E-08028 Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Cano
authors.affiliation: Departament de Biologia, Universitat de Girona , E-17071 Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Massaguer
authors.affiliation: Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, IBUB, Universitat de Barcelona , E-08028 Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Marchán
mesh_terms: D002853:Chromatography, Liquid; D003374:Coumarins / Q000737:chemistry; D016503:Drug Delivery Systems; D008027:Light; D009842:Oligopeptides / Q000737:chemistry*; D010782:Photolysis; D013057:Spectrum Analysis
chemical_list: D003374:Coumarins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C030123:coumarin