Voitenko V G, Bayramashvili D I, Zebrev A I, Zinchenko A A
Institute of Immunology, All-Union Research Institute of Antibiotics, Moscow, USSR.
Agents Actions. 1990 Apr;30(1-2):153-6. doi: 10.1007/BF01969025.
The relationship between the structures of polymyxins and their histamine releasing action on rat mast cells was studied. Analogues of polymyxin B (PB) had different hydrophobic properties, positive charge and peptide chains (deca-, nona- and heptapeptides). The biologic activities of cyclic and decyclic heptapeptides (analogues of PB), and polymyxin M and its decyclic form were investigated. Removal of some amino acid residues from the polymyxin peptide chain decreased but did not completely block its histamine releasing action. There a correlation between the hydrophobicity of the investigated compounds (calculated by Rekker's method) and their histamine releasing action. The native forms of polymyxin M and cyclic heptapeptide (analogue of PB) possessed a higher histamine releasing action compared to their decyclic forms. Modification of PB did not change its noncytotoxic secretagogue properties. These data suggest that hydrophobicity and the cyclic ring are important features in determining the histamine releasing properties of the polymyxins.
