Lipophilic enantiomers of desacetylglucosamine muramyl dipeptide with anti-inflammatory and growth promoting activity
Compositions of matter and methods to reduce inflammation in vertebrates and to promote growth and feed conversion in animals by administering an effective amount of a composition containing a mirror image molecule (enantiomer) of a lipophilic muramyl dipeptide (MDP) derivative that does not contain the N-acetylglucosamine moiety of MDP (i.e., a desmuramyl dipeptide).
1 . An oligopeptide of the following formula:
or a pharmaceutically acceptable acid or salt thereof, wherein:
R 1 is C 1 -C 18 linear alkyl or substituted or unsubstituted aryl;
R 2 , R 3 , and R 4 are each independently selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted aryl;
R 5 is H, unsubstituted alkyl, or substituted or unsubstituted aryl; and
X is O or NR 6 , wherein R 6 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
2 . The oligopeptide of claim 1 , wherein X is O.
3 . The oligopeptide of claim 1 , wherein the oligopeptide has the following structure:
4 . The oligopeptide of claim 1 , wherein the oligopeptide has the following structure:
wherein
R 7 is substituted or unsubstituted alkyl or substituted or unsubstituted aryl; and
Y is O or NR 8 , wherein R 8 is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl.
5 . The oligopeptide of claim 1 , wherein the oligopeptide is L -lactate- D -alanine- L -glutamine-hexadecyl ester.
6 . A pharmaceutical composition comprising at least one oligopeptide of claim 1 and a pharmaceutically acceptable carrier.
7 . A composition comprising at least one oligopeptide of claim 1 and animal feed.
8 . The composition of claim 7 , wherein the at least one oligopeptide is present in the composition in an amount of from about 0.01 mg/kg to 5 mg/kg.
9 . The composition of claim 7 , wherein the composition further comprises an additive used in an animal diet.
10 . The composition of claim 9 , wherein the additive comprises an enzyme, a probiotic, a prebiotic, an antioxidant, an antibiotic growth promoter, a coloring agent, or a combination thereof.
11 . A method for reducing intestinal inflammation in a human, comprising:
administering the pharmaceutical composition of claim 6 to a human having intestinal inflammation, wherein the administration reduces the intestinal inflammation.
12 . A method for promoting growth in an animal, comprising:
administering the oligopeptide of claim 1 to an animal, wherein the administration enhances the growth of the animal.
13 . A method for promoting growth in an animal, comprising:
administering the composition of claim 7 to an animal, wherein the administration enhances the growth of the animal.
14 . A method for enhancing feed conversion in an animal, comprising:
administering the oligopeptide of claim 1 to an animal, wherein the administration enhances the feed conversion of the animal.
15 . A method for enhancing feed conversion in an animal, comprising:
administering the composition of claim 7 to an animal, wherein the administration enhances the feed conversion in the animal.
16 . The oligopeptide of claim 1 , wherein R 5 is H.
17 . The method of claim 11 , further comprising selecting a human having a disease or condition associated with intestinal inflammation.
18 . The method of claim 17 , wherein the disease or condition associated with intestinal inflammation comprises inflammatory bowel disease, irritable bowel syndrome, Crohn's disease, ulcerative colitis, or a bacterial infection.