Application of Stereocontrolled Stepwise [3+2] Cycloadditions to the Preparation of Inhibitors of α4β1-Integrin-Mediated Hepatic Melanoma Metastasis

✍ Scribed by Aizpea Zubia; Lorea Mendoza; Silvia Vivanco; Eneko Aldaba; Teresa Carrascal; Begoña Lecea; Ana Arrieta; Tahl Zimmerman; Fernando Vidal-Vanaclocha; Fernando P. Cossío

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 501 KB
• Volume: 44
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200462497

✦ Synopsis

Intravascular circulation of cancer cells represents a frequent event along neoplasic progression that seriously increases the probability of occurrence of metastasis. However, the adhesion of blood-borne cancer cells to the microvascular wall is a prerequisite for metastatic cell implantation at target organs. Similar to capillary homing of leukocytes, this process is proinflammatory cytokine-inducible and the mechanism involves specific binding between cancer and endothelial cell adhesion molecules. [1] Previously, we and others reported that integrin "very late antigen 4" (VLA-4, a 4 b 1 ) accounts for melanoma cell adhesion to endothelium in metastasized organs. [2] As vascular adhesion cell molecule 1 (VCAM-1) is the natural ligand of VLA-4, the VLA-4-VCAM-1 interac-