Issue 20, 2014

Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting αvβ3vβ5 integrins and IAP proteins

Abstract

The rational design, synthesis and in vitro biological evaluation of dual action conjugates 11–13, containing a tumour targeting, integrin αvβ3vβ5 ligand portion and a pro-apoptotic SMAC mimetic portion (cyclo-RGD/SMAC mimetic conjugates) are reported. The binding strength of the two separate units is generally maintained by these dual action conjugates. In particular, the connection between the separate units (anchor points on each unit; nature, length and stability of the linker) influences the activity of each portion against its molecular targets (integrins αvβ3vβ5 for cyclo-RGD, IAP proteins for SMAC mimetics). Each conjugate portion tolerates different substitutions while preserving the binding affinity for each target.

Graphical abstract: Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting αvβ3/αvβ5 integrins and IAP proteins

Supplementary files

Article information

Article type
Paper
Submitted
26 Jan 2014
Accepted
21 Mar 2014
First published
21 Mar 2014
This article is Open Access
Creative Commons BY-NC license

Org. Biomol. Chem., 2014,12, 3288-3302

Author version available

Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting αvβ3vβ5 integrins and IAP proteins

M. Mingozzi, L. Manzoni, D. Arosio, A. Dal Corso, M. Manzotti, F. Innamorati, L. Pignataro, D. Lecis, D. Delia, P. Seneci and C. Gennari, Org. Biomol. Chem., 2014, 12, 3288 DOI: 10.1039/C4OB00207E

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