The main diseases currently driving the therapeutic use of peptide drugs are metabolic diseases (especially T2DM and obesity) and oncology. Peptide drugs are mostly administered by injection. Alternative administration routes are gaining interest including oral and intranasal administration. For this, it is important to improve the stability of peptides and to increase their penetration through the blood-brain barrier and into cells.
To achieve these goals, we developed a new approach to prepare multifunctional peptide-coated gold nanoparticles (Pepte-AuNPs) by a simple one-pot process in which tyrosine functions as reductant to reduce AuCl4 and CALNN is used to stabilize the resulting Pep-AuNPs in aqueous solution via the sulfhydryl group of cysteine. Grafting of the peptide chain to the gold surface prevents irreversible aggregation and allows for direct conjugation to the gold particles by stable S-Au bonds. The peptide also contains a binding domain that reduces choloroaurate ions and allows for biomolecular recognition.
To demonstrate the effectiveness of the peptide-coating, MALDI-TOF/TOF mass spectrometry was employed. The intact, singly, and doubly gold-bound (y1, y2, and a3 ions) peptide CDR of Angiotensin II were analyzed on an Applied Biosystems Voyager DE PRO MALDI-TOF/TOF instrument equipped with a delayed extraction positive ion mode. CID data indicate that Cys is the preferred gold bonding site, which differs from the Zn ion (His) and Cu ion (Arg) bonding sites in angiotensin II, supporting our hypothesis. Moreover, the peptide-gold complexes are very stable under harsh conditions such as high pH and salt concentrations.