The rational design, synthesis and in vitro biological evaluation of dual action conjugates 11-13, containing a tumour targeting, integrin a(v)beta(3)/a(v)beta(5) 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 a(v)beta(3)/a(v)beta(5) for cyclo-RGD, IAP proteins for SMAC mimetics). Each conjugate portion tolerates different substitutions while preserving the binding affinity for each target.
Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting αvβ3/αvβ5 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, C. Gennari. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 12:20(2014), pp. 3288-3302. [10.1039/c4ob00207e]
Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting αvβ3/αvβ5 integrins and IAP proteins
M. MingozziPrimo
;A. Dal Corso;L. Pignataro;P. Seneci;C. GennariUltimo
2014
Abstract
The rational design, synthesis and in vitro biological evaluation of dual action conjugates 11-13, containing a tumour targeting, integrin a(v)beta(3)/a(v)beta(5) 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 a(v)beta(3)/a(v)beta(5) for cyclo-RGD, IAP proteins for SMAC mimetics). Each conjugate portion tolerates different substitutions while preserving the binding affinity for each target.File | Dimensione | Formato | |
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