Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting αvβ3/α vβ5 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

Research output: Contribution to journalArticlepeer-review

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 αvβ3/ αvβ5 for cyclo-RGD, IAP proteins for SMAC mimetics). Each conjugate portion tolerates different substitutions while preserving the binding affinity for each target.

Original languageEnglish
Pages (from-to)3288-3302
Number of pages15
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number20
DOIs
Publication statusPublished - May 28 2014

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

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