Retro-inverso peptides derived from interleukin-3

Abstract

The invention provides methods of treatment using retro-inverso peptides derived from interleukin-3 (IL-3) having between 12 and about 40 amino acids and including the sequence that is retro-inverso with respect to SEQ ID NO: 1. The peptides of the invention have the same activity as native IL-3 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 promoting neurite outgrowth or myelination in a mammal in need thereof comprising the step of administering to said mammal an effective, neurite outgrowth or myelination-facilitating amount of a composition comprising isolated retro-inverso peptide having between 12 and about 40 amino acids, wherein said peptide comprises the sequence D-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile and a pharmaceutically acceptable carrier. 
     
     
         2 . The method of  claim 1 , wherein said retro-inverso peptide consists of the sequence D-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile. 
     
     
         3 . The method of  claim 1  or  2 , wherein said mammal is a human. 
     
     
         4 . The method of  claim 1  or  2 , wherein said administering step is selected from the group consisting of direct local injection, systemic, intracranial, intracerebrospinal, topical and oral. 
     
     
         5 . A method for stimulating hematopoiesis comprising contacting pluripotential hematopoietic stem cells with an effective, hematopoiesis-stimulating amount of a composition comprising isolated retro-inverso peptide having between 12 and about 40 amino acids, wherein said peptide comprises the sequence D-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile and a pharmaceutically acceptable carrier. 
     
     
         6 . The method of  claim 5 , wherein said retro-inverso peptide consists of the sequence D-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile. 
     
     
         7 . The method of  claim 5  or  6 , wherein said method results in the generation and differentiation of cells selected from the group consisting of macrophages, neutrophils, eosinophils, basophils, mast cells, megakaryocytes and erythroid cells. 
     
     
         8 . A method for promoting neurite outgrowth or myelination in a mammal in need thereof comprising the step of administering to said mammal an effective, neurite outgrowth or myelination-facilitating amount of a composition comprising isolated retro-inverso peptide having between 12 and about 40 amino acids, wherein said peptide comprises the sequence D-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile, 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, carboxy terminus, or both amino and carboxy 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-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile. 
     
     
         10 . The method of  claim 8  or  9 , wherein said mammal is a human. 
     
     
         11 . The method of  claim 10 , wherein said administering step is selected from the group consisting of direct local injection, systemic, intracranial, intracerebrospinal, topical and oral. 
     
     
         12 . A method for stimulating hematopoiesis comprising contacting pluripotential hematopoietic stem cells with an effective, hematopoiesis-stimulating amount of a composition comprising isolated retro-inverso peptide having between 12 and about 40 amino acids, wherein said peptide comprises the sequence D-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile, 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, carboxy terminus, or both amino and carboxy 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. 
     
     
         13 . The method of  claim 12 , wherein said retro-inverso peptide consists of the sequence D-Leu-D-Asn-D-Pro-D-Arg-D-Arg-D-Leu-D-Asn-D-Asn-D-Glu-D-Met-D-Leu-D-Ile. 
     
     
         14 . The method of  claim 12  or  13 , wherein said method results in the generation and differentiation of cells selected from the group consisting of macrophages, neutrophils, eosinophils, basophils, mast cells, megakaryocytes and erythroid cells.