Non-amyloidogenic peptide tags for the regulatable self-assembling of protein-only nanoparticles

Targeting low-density lipoprotein receptors with protein-only nanoparticles

“…Such organization had been previously proved useful in promoting the spontaneous formation of highly stable fluorescent protein nanoparticles, provided a sufficient positive electrostatic charge is present at the N terminus of the whole fusion (Cespedes et al, 2014;Unzueta et al, 2012).…”

“…When fused to the amino terminus of a His tagged GFP, the cationic peptide ApoB promotes the formation of nanoparticles that are only composed by the modular protein acting as self-interacting 365 building block. This is based on a recently proposed protein engineering principle that allows designing protein nanoparticles by the fusion of cationic peptides to polyhistidine tagged polypeptides, and that act irrespective of the nature and sequence of the core protein (Cespedes et al, 2014;Unzueta et al, 2012). Nanoparticle formation is promoted by the hydrostatic contacts between the resulting dipolar monomers, but the 370 whole supramolecular structure is largely stabilized by additional forces such as Van der Waals, hydrogen bond interactions (Cespedes et al, 2014;Unzueta et al, 2014), and protein-DNA interactions if used as non-viral gene therapy vehicle .…”

“…In a preliminary screening (Unzueta et al, 2012), Angiopep-2 and Seq-1 were observed as unable to promote the assembling of the fusion proteins in higher order nanoparticles, probably due to their low cationic amino acid content, although doubts remained about the potential influence of the composition of the different buffers used to store the proteins. All the proteins produced here were tested again for nanoparticle…”

“…Being ApoB a well-known BBB-crossing peptide for soluble drugs (Kreuter et al, 2002b) and also when linked to nanoparticles (Kim et al, 2007) (Cespedes et al, 2014;Unzueta et al, 2012) and also for ligand-mediated cell penetrability (Figure 3 and 440 4), the most complex biological barriers imposed by brain vessels might represent a tighter bottleneck to proper biodistribution.…”

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles

“…In previous studies, we have developed a protein engineering platform to promote the self-assembly of modular GFP constructs, based on the combination of end-terminal cationic stretches and polyhistidines [17,18]. Driven by electrostatic interactions and with a strong involvement of the histidine-rich tail, these peptides promote the formation of stable oligomers of defined average size in the nanoscale irrespective of the amino acid sequence and origin of the core protein placed in between.…”