Enhancing the biological activity of polyoxometalate-peptide nano-fibrils by spacer design

Abstract

Polyoxometalates (POMs) and peptides can be conjugated to yield novel bio-hybrids with potential application as nanodrugs. However, the observed POM-induced folding of the peptide prevents its availability towards biological targets. An Anderson-Evans POM was functionalized with a bombesin analog peptide and engineered by adding a tailored hydrophilic and anionic spacer between the two moieties, to make the targeting sequence more accessible and enable an unprecedented cancer cell recognition capability.

Fig. 1. Reaction scheme to obtain POMs 6 and 7, showing the different impact of the spacer on the peptide secondary structure (evolving into α-helix for 6 and to random coil for 7). For graphical reasons, only one side of the bis-functionalized POM is shown. Countercations (TBA) are also omitted. DCC = N,N′-dicyclohexylcarbodiimide; DIPEA = N,N-diisopropylethylamine.

Fig. 2. Comparison of chemical shift (400 MHz COSY spectra in d₆-DMSO) for NH–CH_α cross peaks belonging to free and POM-grafted DB (peptide 1 (red), POM 6 (green), POM 7 (blue)).

Fig. 3. Far-UV CD spectra of peptide 2 (53 μM, dot line) and POM–(peptide)₂7 (26.5 μM, solid line) at different TFE : water percentage (10% black line, 80% red line).

Fig. 4. TEM images collected from 0.2 mM solutions in H₂O with 3% DMSO of 7, scale bar of 100 nm (a) and 6, scale bar 500 nm (b).