Tryptophan as a functional replacement for ADP-ribose-arginine in recombinant proteins
AssigneesThe United States of America, as represented by the Secretary, Department of Health and Human Services, University of Massachusetts
InventorsJoel Moss, Linda Stevens, Christelle Bourgeois, Rita Bortell
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Abstract
A method is disclosed for producing a polypeptide with a modified activity or stability, by replacing an arginine residue capable of being ADP-ribosylated with a tryptophan or a phenylalanine. In one embodiment, compositions are provided that include polypeptides, such as alpha defensin, with arginine-to-tryptophan or arginine-to-phenylalanine substitutions, where the arginine residue is capable of being ADP-ribosylated. In another embodiment, methods are disclosed for modifying an immune response in a subject.
Claims23
A substituted human defensin polypeptide, comprising :
- (i) a tryptophan residue or a phenylalanine residue substituted for at least one arginine residue in a corresponding non-substituted human alpha-defensin or human beta-defensin polypeptide;
- (ii) six conserved cysteine residues that form three disulfide bonds;
- (iii) decreased cytotoxic activity, compared to the corresponding non-substituted human defensin polypeptide;
- and
- (iv) increased polypeptide stability, compared to the corresponding non-substituted human defensin polypeptide, wherein the at least one arginine residue in the corresponding non-substituted human defensin polypeptide is ADP-ribosylated,
- wherein the polypeptide is no more than 94 amino acids in length and retains anti-microbial activity.
Dependencies are inferred from the claim text.