Monodisperse silicate nanoparticles have been used for the development of a site-specific ligation method that enables the control of the biomolecule orientation at the solid–liquid interface. Two types of zeolite nanoparticles were studied: zeolite β, which possesses a Si/Al ratio of 25, and silicalite-1, which is a fully silicic material. Zeolite-type materials are microporous silicate with pores of a well-defined size ranging from 2 to 20 Å. Semicarbazide-functionalized silicate colloids have been prepared for the site-specific ligation of COCHO-modified polypeptides. The obtained colloidal suspensions have been characterized by complementary techniques providing information on the size distribution, morphology, and porosity of the particles and chemical nature of the grafting. The specificity of the particles’ surface for the semicarbazide group has been studied by fluorescence spectroscopy with two peptides labeled with rhodamine. A first peptide bares a COCHO functionality, which should bind covalently with the semicarbazide surface. The second peptide bares an amine end-group, which should interact by nonspecific adsorption with the surface. The results demonstrated that the peptide/colloids’ reactivity is dramatically influenced by the chemical composition of the particles’ surface. Indeed, while zeolite β (aluminosilicate) particles react indifferently with the two peptides, silicalite particles (pure silicate) anchor exclusively the peptide bearing the COCHO functionality. This particular physisorption phenomenon of zeolite β is attributed to the aluminum atoms present at the particles’ surface, which have a specific affinity for peptides. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)