Some physicochemical properties of 7-oxoacyl-L-alanyl-D-isoglutamines.
N-(7-Oxoacyl)-L-alanyl-D-isoglutamines are substances with similar effects on immune system as N-acetylmuramyldipeptide (MDP). They were synthesized to eliminate some side effects of MDP: pyrogenicity, leucopenia, hypertension and fast elimination from the body. The aim of our work was to determine some physicochemical properties of a series of N-(7-oxoacyl)-L-alanyl-D-isoglutamines, that have zero to six methylene groups between terminal methyl and 7-oxo group. The following properties were examined: water solubility, lipophilicity, thermal behaviour and true density. The results were compared and it was established that the lipophilic parameter determined by high-performance liquid chromatography is increasing by the increase of alkyl chain while the water solubility is decreasing at the same time. In both cases the substance with the longest chain (N-(7-tetrakanoyl)-L-alanyl-D-isoglutamine) is an exception. The lipophilic parameter of this substance is lower and water solubility higher than with the substances with three, four and five methylene groups between terminal methyl and 7-oxo group. These results can be explained by the twisted conformation of N-(7-tetrakanoyl)-L-alanyl-D-isoglutamine molecule in water solution. By means of thermal analysis it was discovered that the melting point is decreasing with the increase of alkyl chain. From the true density and melting enthalpy measurements it is evident that with the increase of alkyl chain the arrangement of molecules in solid state is increasing up to the molecule with four methylene groups between terminal methyl and 7-oxo group. Substances with longer chains have lower true density and melting enthalpy because of the different arrangements of the molecules.
Planinsek
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University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000, Ljubljana, Slovenia.
Srcic
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D000276:Adjuvants, Immunologic / Q000737:chemistry*; D003460:Crystallization; D005973:Glutamine / Q000031:analogs & derivatives* / Q000737:chemistry; D008968:Molecular Conformation; D012995:Solubility
D000276:Adjuvants, Immunologic; D005973:Glutamine; C059858:isoglutamine