Hampered Binding to Blood Serum Proteins and the Biological Activity of Antimicrobial Peptide Containing N3-(4-Methoxyfumaroyl)-L-2,3-Diaminopropanoic Acid Immobilized on Magnetic Nanoparticles

• Published in: Pharmaceutical chemistry journal 2018-02, Vol.51 (11), p.985-994
• Main Authors: Nowak-Jary, Julia, Gronczewska, Ewelina, Worobiec, Weronika
• Format: Article
• Language: English
• Subjects: Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-018-1728-2

Peptides containing N 3 -(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP) are known as antifungal and antibacterial agents. However, FMDP peptides bind to the blood serum proteins in an irreversible way thereby losing their biological activity. In the present work, one of the most potent FMDP peptides, LysNvaFMDP, was immobilized on iron-oxide(II/III) magnetic nanoparticles (MNPs) in order to obtain a potentially more resistant form of this compound capable of binding to proteins. The obtained nanostructures were characterised using FT-IR and DLS techniques. Then, the degree of binding of the immobilized FMDP agent to albumin from bovine pancreas and to the proteins from human blood serum was tested using UV-VIS spectrophotometric method in comparison to the unbound form of this peptide. Microbial growth inhibition tests were also carried out. The form of LysNvaFMDP immobilized on MNPs turned out to have lower affinity to the proteins in comparison to the unbound form and, as a result, it showed a higher antimicrobial activity against Lactobacillus acidophilus ATCC 4356 strain. The immobilized form of FMDP agent is significantly protected from binding to albumin and other blood serum proteins and thus retains its antimicrobial activity. It is possible that such a form of this agent will reach clinics.