Activity of Homocarnosine and Other Compounds Against Staphylococcal Infections in Mice

Abstract

Homocarnosine and carnosine have been identified in bovine brain extracts which are effective in protecting mice against infections by Staphylococcus aureus. These peptides, as well as L-histidine, L-1-methylhistidine, f-alanine, y-aminobutyric acid, 6-aminovaleric acid, E-aminocaproic acid, 1-aminomethylcyclohexane-4-carboxylic acid, and anserine, were tested as prophylactic agents against S. aureus infections in C3H and Swiss mice. Histidine and methylhistidine were ineffective in preventing mortality in both mouse strains. Carnosine, anserine, and e-aminocaproic acid were effective in C3H but not in Swiss mice. #-Alanine and ,y-aminobutyric acid were weakly effective (C3H) or ineffective (Swiss). 3-Aminovaleric and 1-aminomethylcyclohexane-4-carboxylic acid (tested only in Swiss) were somewhat effective in early stages of the infection. Homocarnosine was the best compound and was highly effective in protecting both mouse strains against S. aureus infections by the testing procedure employed.

Prophylactic Effects of γ-Aminobutyrylhistidine (Homocarnosine) on Experimental Staphylococcal Infections in Mice

“…Peptide and its component amino acids. Previous work (15) showed that whereas homocarnosine protected animals against infections, its components, L-histidine and y-aminobutyric acid, by themselves were ineffective in Swiss mice with the dosage schedule used. Therefore experiments were undertaken to determine (i) the effect of a mixture of the two component amino acids in equimolar concentrations and (ii) the effect of a combination of homocarnosine with any one of the components.…”

“…Although the physiological function of homocarnosine is still speculative, the present studies have shown its ability to induce resistance to staphylococcal infections in mice. Tanaka et al (15,16) reported that the dipeptides, L-carnosine, homocarnosine and anserine, possess antistaphylococcal properties in C3H mice and proposed that the protective value of brain extract may in part be ascribed to these peptides or compounds related to them. Although we confirmed the antistaphylococcal property of homocarnosine, we did not find such activity for carnosine or anserine in Swiss albino mice, except perhaps in the early stages of infection, under the conditions of assay (15).…”

“…Tanaka et al (15,16) reported that the dipeptides, L-carnosine, homocarnosine and anserine, possess antistaphylococcal properties in C3H mice and proposed that the protective value of brain extract may in part be ascribed to these peptides or compounds related to them. Although we confirmed the antistaphylococcal property of homocarnosine, we did not find such activity for carnosine or anserine in Swiss albino mice, except perhaps in the early stages of infection, under the conditions of assay (15). The sphingolipids, sphingomyelin and phrenosin, were also essentially ineffective, although they, too, had displayed activity in C3H mice (N. J. Berberich, Jr., Ph.D. Thesis, Institutum Divi Thomae, Cincinnati, Ohio, 1965).…”

“…Previous reports from our laboratories dealt with the effectiveness of beef brain extract against Staphylococcus aureus infections in mice (8)(9)(10)(11). A number of compounds found in brain extract (16) or compounds related to them were tested for their ability to protect mice against S. aureus infections, and, in a preliminary report, we found that My-aminobutyrylhistidine (homocamosine) was the best of the compounds examined (15). Homocarnosine was previously found to be present exclusively in the central nervous system (1,13).…”

Effects of ω-Amino Acids and Related Compounds on Staphylococcal Infections in Mice: a Combined Prophylactic-Therapeutic Procedure 1

“…p. 283, 1964. Further studies with the amino acid analyzer and an Amberlite CG-120, 2,6-lutidine column followed by a diazo-coupling reaction confirmed the presence of carnosine and homocarnosine in the bovine extract (11,12).…”