Anti-trypanosomal peptides and uses thereof
AssigneeUniversity of George Research Foundation, Inc.
InventorsJohn M. Harrington, Stephen L. Hajduk
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Abstract
The present invention provides methods of killing, inhibiting the growth, and/or inhibiting the reproduction of kinetoplastid protozoan with hydrophobic signal sequence peptides and compositions including such hydrophobic signal sequence peptides.
Claims36
A method of inducing rigidification of the plasma membrane of a bloodstream form of a kinetoplastid protozoan of the genus Trypanosoma, the method comprising contacting the protozoan with an isolated hydrophobic signal sequence peptide, wherein the isolated hydrophobic signal sequence peptide consists of 17 to 25 amino acid residues of an uncleaved, hydrophobic N-terminal signal sequence, wherein the isolated hydrophobic signal sequence peptide contains a positively charged amino acid at position minus five relative to the C-terminus of the hydrophobic signal sequence peptide, and wherein the hydrophobic signal sequence peptide comprises at least nine consecutive amino acid residues of MSDLGAVISLLLWGRQLFA, SEQ ID NO:1 or a derivative of SEQ ID NO:1, wherein the derivative of SEQ ID NO:1 has up to four hydrophobic amino acid residues of SEQ ID NO:1 exchanged for another hydrophobic amino acid, and/or one positively charged amino acid residues of SEQ ID NO:1 exchanged for another positively charged amino acid.
A method of inducing rigidification of the plasma membrane of a bloodstream form of a kinetoplastid protozoan of the genus Trypanosoma, the method comprising contacting the protozoan with an isolated hydrophobic signal sequence peptide, wherein the isolated hydrophobic signal sequence peptide consists of 17 to 25 amino acid residues of an uncleaved, hydrophobic N-terminal signal sequence, wherein the isolated hydrophobic signal sequence peptide contains a positively charged amino acid at position minus five relative to the C-terminus of the hydrophobic signal sequence peptide, and wherein the hydrophobic signal sequence peptide comprises at least nine consecutive amino acid residues of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:15, SEQ ID NO:16 or SEQ ID NO:17.
A method of inducing rigidification of the plasma membrane of a bloodstream form of a kinetoplastid protozoan of the genus Trypanosoma, the method comprising contacting the protozoan with an isolated hydrophobic signal sequence peptide, wherein the isolated hydrophobic signal sequence peptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:15, SEQ ID NO:16 and SEQ ID NO:17.
A method of inducing rigidification of the plasma membrane of a bloodstream form of a kinetoplastid protozoan of the genus Trypanosoma, the method comprising contacting the protozoan with an isolated trypanocidal peptide of 12 to 25 amino acid residues in length, wherein the isolated trypanocidal peptide comprises at least nine consecutive amino acid residues of MSDLGAVISLLLWGRQLFA, SEQ ID NO:1 or a derivative of SEQ ID NO:1, wherein the derivative of SEQ ID NO:1 has up to four hydrophobic amino acid residues of SEQ ID NO:1 exchanged for another hydrophobic amino acid, and/or one positively charged amino acid residues of SEQ ID NO:1 exchanged for another positively charged amino acid.
Dependencies are inferred from the claim text.