Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Kubas, Holger [VerfasserIn]   i
 Schäfer, Martin [VerfasserIn]   i
 Bauder-Wüst, Ulrike [VerfasserIn]   i
 Eder, Matthias [VerfasserIn]   i
 Oltmanns, Dörte [VerfasserIn]   i
 Haberkorn, Uwe [VerfasserIn]   i
 Mier, Walter [VerfasserIn]   i
 Eisenhut, Michael [VerfasserIn]   i
Titel:Multivalent cyclic RGD ligands
Titelzusatz:influence of linker lengths on receptor binding
Verf.angabe:Holger Kubas, Martin Schäfer, Ulrike Bauder-Wüst, Matthias Eder, Dörte Oltmanns, Uwe Haberkorn, Walter Mier, Michael Eisenhut
E-Jahr:2010
Jahr:24 July 2010
Umfang:7 S.
Fussnoten:Gesehen am 07.03.2023
Titel Quelle:Enthalten in: Nuclear medicine and biology
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1993
Jahr Quelle:2010
Band/Heft Quelle:37(2010), 8, Seite 885-891
ISSN Quelle:1872-9614
Abstract:Peptides involving the RGD motive (arginine-glycine-aspartic acid) recognize members of the integrin receptor family. Since the receptors are located mainly on the surface of endothelial cells, structural modifications including multimers of c(RGDfE) were recently found to improve the binding avidity for αvβ3 integrin significantly. The multivalent RGD peptides exhibited rather loose linkages partly including oligo(ethylene glycol) spacers (EGn) with different chain lengths. Therefore, the dependence of multivalent RGD systems with and without EGn linkers were investigated on their binding properties to cultured αvβ3 integrin-expressing U87MG cells. - Methods - We synthesized a series of di-, tri- and tetravalent rigid scaffolds (terephthalic acid, trimesic acid and adamantane-1,3,5,7-tetracarboxylic acid) conjugated to c(RGDyK) ligands, which were linked contiguously or separated by the oligo(ethylene glycol) spacers. The inhibition constants of these c(RGDyK) derivatives were determined by competition assays with 125I-labeled echistatin. - Results - While c(RGDyK) function is a relative weak competitor against [125I]echistatin (Ki, 329±18 nM) for αvβ3 integrin-expressing U87MG cells, RGD dimers improved the competition potency considerably (Ki, 64±23 nM). This effect was even more pronounced with the RGD trimers (Ki, 40±7 nM) and tetramers (Ki, 26±9 nM). The introduction of EGn spacers and the increase of linker lengths proved to be detrimental since more competitors were needed to compete with [125I]echistatin. The EG6 group, for example, reduced the inhibition constants by 29% (dimer), 57% (trimer) and 97% (tetramer). - Conclusion - The binding experiments performed with the three forms of multivalent RGD ligands indicate the weakening of competitive potency against [125I]echistatin with the introduction of EGn spacers. This effect may be related to the decrease of the effective RGD molarity, which becomes most prominent within the tetravalent series.
DOI:doi:10.1016/j.nucmedbio.2010.06.005
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.nucmedbio.2010.06.005
 Volltext: https://www.sciencedirect.com/science/article/pii/S0969805110003112
 DOI: https://doi.org/10.1016/j.nucmedbio.2010.06.005
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Angiogenesis
 Linker length
 Multivalency
 Peptides
 αβ integrin
K10plus-PPN:1838457151
Verknüpfungen:→ Zeitschrift

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/69048731   QR-Code
zum Seitenanfang