Selektive Bildgebung der angiogenetisch relevanten Integrine α5β1 und αvβ3

Abstract

Diagnose und Therapie: Derivate der für die beiden angiogenetisch relevanten Integrine α5β1 und αvβ3 selektiven Antagonisten 1 bzw. 2 können Tumorzellen mit unterschiedlichen Integrinmustern in vivo selektiv ansprechen und das Tumorwachstum in vivo verzögern. Weiterhin wurde der erste α5β1‐selektive Integrinantagonist entwickelt, der die spezifische molekulare Bildgebung mit Positronenemissionstomographie ermöglicht.

Bioconjugation of Supramolecular Metallacages to Integrin Ligands for Targeted Delivery of Cisplatin

“…19 Over the years, numerous small peptidic or peptidomimetic molecules were designed and used to selectively address various integrin sub-types to treat different pathologies or for imaging. [20][21][22][23][24][25][26] As an example, the cyclic pentapeptide cyclo(RGDfV) 27 and the related Cilengitide 28 were found to be potent ligands for the integrins αvβ3, αvβ5, and α5β1. 25,29 It is worth mentioning that direct tethering of integrin binding peptides to cytotoxic platinum complexes have been also reported.…”

“…Integrins have been extensively studied as drug targets, interacting with the extracellular matrix (ECM) and thereby regulating many cellular functions, such as proliferation, migration, and survival. , In mammals, there are eight RGD recognizing integrin subtypes, among them αvβ3 and α5β1, expressed in cancer tissue and promoting tumor metastasis . Over the years, numerous small peptidic or peptidomimetic molecules were designed and used to selectively address various integrin subtypes to treat different pathologies or for imaging. − As an example, the cyclic pentapeptide cyclo (RGDfV) and the related Cilengitide were found to be potent ligands for the integrins αvβ3, αvβ5, and α5β1. , …”

“…Hence, we conjugated a Pd 2 L 4 metallacage to four integrin ligands for subtype specific targeting of integrin αvβ3 (compounds 1 – 3 ) ,, or α5β1 (compound 4 ), respectively (Figure ). ,,, Cage formation and cisplatin encapsulation were studied by NMR spectroscopy. The conjugated cages were first studied for their integrin recognition properties using an ELISA assay.…”

“…Compounds 1 – 4 are the integrin binding ligands for αvβ3 ( 1 – 3 ) and α5β1 ( 4 ). The integrin ligands were originally described in the following literature: 1 , , 2 , , 3 , and 4 . , …”