Advances in Biochemistry
Volume 6, Issue 5, October 2018, Pages: 39-46
Received: Oct. 25, 2018;
Accepted: Nov. 9, 2018;
Published: Dec. 14, 2018
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Nurit Beyth, Department of Prosthodontics, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Edna Blotnick-Rubin, Department of Medical Neurobiology, Institute for Medical Research-Israel–Canada, Hebrew University of Jerusalem, Jerusalem, Israel
Yael Houri-Haddad, Department of Prosthodontics, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Shaul Beyth, Orthopedic Surgery Complex, Hadassah University Hospital, Jerusalem, Israel
Andras Muhlrad, Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Buforin is a cationic antimicrobial peptide (AMP) from the stomach of toads. Buforin II is a derivative of this naturally occurring peptide. Buforin IIB is a synthetic analog of buforin II containing a model α-helical sequence (3xRLLR) at the C-terminus. To further increase the antimicrobial activity and decrease toxicity to eukaryotic cells, new derivatives (buforin III analogs) were designed by substituting amino acids in the buforin IIB sequence. In this work, the antimicrobial activity and the actin- and DNA-binding characteristics of buforin IIIB (RVVRQWPIGRVVRRVVRRVVR) and the newly synthetized buforin IIIE (RLLLRQWPIGRLLRRLLRRLLR) were studied. The antimicrobial activity of buforin IIIB (measured against E. coli and E. faecalis) was significantly greater than that of buforin IIIE, while both peptides were nontoxic to macrophages at the minimal concentrations required to inhibit microbial growth. Actin, which inhibited the antimicrobial activity of the two buforin III analogs, was bundled by both peptides; however, less buforin IIIE than buforin IIIB was needed for bundling. Higher levels of NaCl were needed to unbundle actin bundled by buforin IIIE than actin bundled by buforin IIIB, which indicates that buforin IIIE binds more strongly to actin than buforin IIIB. Actin bundled by either peptide was dissociated with the same concentration of DNA; however, buforin IIIE bound more strongly to DNA than buforin IIIB. These results contribute to the understanding of the antimicrobial mechanism of cationic AMPs in general and histone-derived peptides in particular.
Buforin III Analogs Bind to DNA and Actin and Inhibit Bacterial Growth, Advances in Biochemistry.
Vol. 6, No. 5,
2018, pp. 39-46.
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