Stereoisomere Peptid‐Bibliotheken und Peptidmimetika zum Design von selektiven Inhibitoren des α_v β₃‐Integrins für eine neuartige Krebstherapie

Abstract

Zell-Zell-und Zell-Matrix-Adhasionen der Blutgerinnung, der Osteoporose und terdrucken die tumorinduzierte Angiospielen eine entscheidende Rolle im bio-dem Krebsgeschehen beteiligt sind. Eine genese (Neubildung von BlutgefaDen) . logischen Geschehen. Sie regeln unter selektive Inhibierung von einzelnen In-Gesundes Gewebe mit ausgebildeten anderem im Rahmen der Signaltrans-tegrin-Subtypen ist daher von eminen-BlutgefaBen wird offenbar nicht tanduktionskaskade das Gleichgewicht tem pharmazeutischem Interesse. Mit ei-giert. Dies eroffnet einen neuen, hoffzwischen Leben und Tod (Apoptose) der nem neuartigen Verfahren zum ,,raum-nungsvollen Weg fur die Tumortherapie. Zelle. Eine wichtige Klasse von Oberfla-lichen Screening" ist es moglich, hochsechenrezeptoren sind die Integrine, von lektive und aktive Inhibitoren fur Inte-Stichworte: Cyclopeptide Integrine * denen eine ganze Reihe von Subtypen grine und speziell fur den a,P,-Subtyp zu Rezeptoren Struktur-Aktivitats-Bezieexistieren, die an verschiedenen biologi-erhalten. Diese a,/&-Antagonisten sind hungen schen Prozessen wie der Embryogenese, im nanomolaren Bereich aktiv und un- Einleitung

Facile Synthesis of Cyclic Tetrapeptides from Nonactivated Peptide Esters on Metal Centers

“…[3] Its synthesis involves several steps as well as the use of CSe 2 and dicyanoacetylene, both difficult reagents to synthesize and use. [3] We report here facile syntheses of the complexes 1 and 2, which [K([2.2.2] …”

“…[1,2] Synthetic cyclopeptides are interesting target molecules owing to their biological activity, their model character for conformational analyses, and their potential as drugs, among other things. [3] Synthetic analogues of hormones [4] show the link between reduced peptide flexibility due to cyclization and increased receptor specificity in a particularly impressive fashion. As the metabolic degradation of peptides begins preferably at the C or N terminals, [1] cyclic peptides are expected to have a longer biological availability than their linear analogues.…”

The Constrained Amino Acid β‐Acc Confers Potency and Selectivity to Integrin Ligands

“…Spatial screening comprises the synthesis of a library of stereoisomeric cyclopeptides in which cyclization leads to restriction of the peptide conformation. A recognition epitope, for example, the RGD sequence, is combined with a secondary-structure-inducing element, for example, a d-amino acid, [4] an N-alkyl-amino acid, [5] or a b-amino acid. [6] The cyclic pentapeptide cyclo-(-Arg-Gly-Asp-d-Phe-Val-) 1 was developed by Kessler and co-workers in a spatial screening approach as a very active and selective ligand of integrin a V b 3 .…”

“…Spatial screening of peptides and peptidomimetics is an important concept in this context. [4] It is applied in the search for an unknown active conformation of a recognition sequence present in a ligand. Spatial screening comprises the synthesis of a library of stereoisomeric cyclopeptides in which cyclization leads to restriction of the peptide conformation.…”

Synthetic Approaches to Study Multivalent Carbohydrate—Lectin Interactions

“…Positional diversity generates different carbohydrate patterns displayed on the scaffolds. Varying the stereochemistry of the amino acids increases spatial diversity by generating different backbone folds [18].…”