Comparative pharmacokinetics and biodistribution of HAEE and HASS peptides

Due to the limited availability of advanced methods to diagnose Alzheimer's disease, small molecules and short peptides capable of specifically biniding β-amyloid are of special interest. The study aimed to perform comparative assessment of pharmacokinetics and biodistribution of two model peptides, HAEE (His-Ala-Glu-Glu) and HASS (His-Ala-Ser-Ser), as potential platforms for the development of diagnostic kits, as well as to determine the relationship between the peptide structure and organotropism. The study involving BALB/c mice (n = 10) was conducted using the fluorescence labeled compounds. We used in vivo IVIS imaging, ex vivo fluorescence microscopy, and pharmacokinetic analysis. The results showed fundamental differences: the negatively charged HAEE was accumulated mainly in the kidney (T½β = 4.39 h) due to tubular reabsorption, while neutral HASS was soon captured by the liver (T½β = 2.76 h). The data obtained demonstrate the key role of amino acid composition in determining organotropism and open prospects for the development of organ-specific peptide systems.