Subject(s)
Aspartame , Cyclopropanes , Dipeptides , Taste , Aspartame/analogs & derivatives , Aspartame/chemical synthesis , Circular Dichroism , Dipeptides/analogs & derivatives , Dipeptides/chemical synthesis , Humans , Indicators and Reagents , Models, Molecular , Molecular Structure , Protein Conformation , Stereoisomerism , Structure-Activity RelationshipABSTRACT
A series of analogues designed to assess the importance of the amide bond in the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester has been synthesized and tested. The peptide bond was methylated, replaced by an ester bond, or reversed. all of these modifications produced compounds that did not have a sweet taste. We conclude that the steric, electronic, and directional characteristics of the amide bond are essential for biological activity in the dipeptide sweeteners.
Subject(s)
Aspartame/analogs & derivatives , Dipeptides/analogs & derivatives , Sweetening Agents/pharmacology , Aspartame/chemical synthesis , Aspartame/pharmacology , Humans , Ions , Molecular Conformation , Structure-Activity Relationship , Sweetening Agents/chemical synthesisABSTRACT
The homocarnosine content and homocarnosine synthetase activity were studied in the brain of rats in normal state and under hyperoxia. The homocarnosine content is higher in phylogenetically old brain areas as compared with that in the cerebral hemispheres. Its nonuniform distribution in the brain is associated with different activity of homocarnosine-carnosine synthetase in the corresponding brain areas. At the preconvulsive stage of oxygen poisoning the homocarnosine content in all the brain areas does not change, the homocarnosine-carnosine synthetase activity is 32% lower. At the convulsive stage of hyperoxia the homocarnosine amount in the cerebral hemisphere decreases by 33%, in the midbrain and diencephalon -- by 70, in the medulla oblongata -- by 60, in the cerebellum -- by 58%. The decrease in the homocarnosine content correlates with that in the activity of homocarnosine-carnosine synthetase in the corresponding brain areas; in the cerebral hemispheres -- by 33%, in the midbrain and diencephalon -- by 50, in the medulla oblongata -- by 49, in the cerebellum -- by 40%.
Subject(s)
Brain/metabolism , Carnosine/analogs & derivatives , Dipeptides/analogs & derivatives , Oxygen/pharmacology , Peptide Synthases/metabolism , Animals , Brain/drug effects , Carnosine/metabolism , Rats , Tissue DistributionSubject(s)
Aminobutyrates/metabolism , Anserine/pharmacology , Brain/metabolism , Carnosine/analogs & derivatives , Carnosine/pharmacology , Dipeptides/analogs & derivatives , Dipeptides/pharmacology , gamma-Aminobutyric Acid/metabolism , 4-Aminobutyrate Transaminase/metabolism , Animals , Brain/drug effects , Brain/ultrastructure , Glutamate Decarboxylase/metabolism , Glutamates/metabolism , In Vitro Techniques , Male , Mitochondria/drug effects , Mitochondria/enzymology , Mitochondria/metabolism , Rats , Synaptosomes/drug effects , Synaptosomes/enzymology , Synaptosomes/metabolismABSTRACT
Several analogs structurally related to aspartame were prepared in order to establish if chemical modifications of the molecule might improve sweetness. None of these analogs exhibited any sweet taste; on the contrary in most cases they were bitter.
Subject(s)
Aspartame/analogs & derivatives , Aspartame/chemical synthesis , Dipeptides/analogs & derivatives , Dipeptides/chemical synthesis , Chemical Phenomena , Chemistry, Physical , Structure-Activity RelationshipABSTRACT
1.-- Synthesis of carcinine was performed by direct condensation of beta-alanine with histamine (free base), in the presence of N-N'-dicyclocarbodiimide. The amine radical of beta-alanine was protected by the t-butoxycarbonyl radical. This fast and simple method yielded a perfectly pure crystalline product. 2.-- Carcinine had no influence upon heartbeat frequency nor on respiratory movements in rats. 3. -- Carcinine had a vasodepressive action upon Vertebrates. It was active at half the concentration of carnosine and at about a thousand times the concentration of histamine. It appeared that histamine lost a great extent of its activity when linked with beta-alanine.
