Retro-inverso peptides derived from interleukin-6

Abstract

This invention provides methods of treatment using retro-inverso peptides derived from interleukin-6 (IL-6) having between 15 and about 40 amino acids, and including the sequence that is retro-inverso with respect to SEQ ID NO 1, i.e. wherein said peptide comprises the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu. The peptides of the invention have the same activity as native IL-6 and also have neurotrophic activity. The peptides of the invention are also less susceptible to proteolytic degradation in vivo because of their D-amino acid linkage.

1 . A method for inhibiting LPS-induced TNF release comprising contacting macrophages with an effective, TNF-inhibiting amount of a composition comprising isolated retro-inverso peptide having between 15 and about 40 amino acids, wherein said peptide comprises the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu and a pharmaceutically acceptable carrier. 
     
     
         2 . The method of  claim 1 , wherein said retro-inverso peptide consists of the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu. 
     
     
         3 . A method for inhibiting LPS-induced TNF release comprising contacting said macrophages with an effective, TNF-inhibiting amount of a composition comprising isolated retro-inverso peptide having between 15 and about 40 amino acids, wherein said peptide comprises the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu, wherein said peptide is optionally modified, said modification selected from a group consisting of glycosylation, reduction of one or more amide bonds, methylation of one or more nitrogens, esterification of one or more carboxylic acid groups, and modification at the amino terminus, carbonyl terminus, or both amino and carbonyl termini with a moiety independently selected from the group consisting of CH 3 CO, CH 3 (CH 2 ) n CO, C 6 H 5 CH 2 CO and H 2 N(CH 2 ) n CO, wherein n=1-10, and a pharmaceutically acceptable carrier. 
     
     
         4 . The method of  claim 3 , wherein said retro-inverso peptide consists of the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein the mammal is a human. 
     
     
         6 . A method for promoting hematopoeisis comprising administering an effective amount of a composition comprising isolated retro-inverso peptide having between 15 and about 40 amino acids, wherein said peptide comprises the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu and a pharmaceutically acceptable carrier. 
     
     
         7 . The method of  claim 6 , wherein said retro-inverso peptide consists of the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu. 
     
     
         8 . A method for promoting hematopoeisis comprising administering an effective amount of a composition comprising isolated retro-inverso peptide having between 15 and about 40 amino acids, wherein said peptide comprises the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu, wherein said peptide is optionally modified, said modification selected from a group consisting of glycosylation, reduction of one or more amide bonds, methylation of one or more nitrogens, esterification of one or more carboxylic acid groups, and modification at the amino terminus, carbonyl terminus, or both amino and carbonyl termini with a moiety independently selected from the group consisting of CH 3 CO, CH 3 (CH 2 ) n CO, C 6 H 5 CH 2 CO and H 2 N(CH 2 ) n CO, wherein n=1-10, and a pharmaceutically acceptable carrier. 
     
     
         9 . The method of  claim 8 , wherein said retro-inverso peptide consists of the sequence D-Glu-D-Ala-D-Met-D-Lys-D-Pro-D-Leu-D-Asn-D-Leu-D-Asn-D-Asn-D-Glu-D-Ala-D-Leu-D-Ala-D-Glu. 
     
     
         10 . The method of any one of  claims 6  to  9 , wherein the mammal is a human.