The United States of America, As Represented by the Secretary, Department of Health and Human Services

University of Massachusetts

Linda Stevens

Joel Moss

Rita Bellis Bortell

Christelle Bourgeois

Rodney L Levine

Disclosed herein are methods of treating a subject with pulmonary disease including administering to the subject a therapeutically effective amount of a polypeptide including at least one arginine residue susceptible to ADP-ribosylation and nicotinamide adenine dinucleotide (NAD). In some embodiments, the polypeptide and/or NAD is administered via inhalation. Also disclosed is a pharmaceutical composition including at least one polypeptide (such as HNP-1) and NAD. The disclosure also provides in vitro methods of producing a polypeptide with altered activity, including contacting the polypeptide with NAD and an arginine-specific mono-ADP-ribosyltransferase (for example, ART1) to produce a polypeptide including at least one ADP-ribosylated arginine residue, incubating the ADP-ribosylated polypeptide under conditions sufficient for conversion of at least one ADP-ribosylated arginine residue to ornithine, and isolating the ornithine-containing polypeptide. Methods of treating a subject with pulmonary disease including administering to the subject a therapeutically effective amount of a modified polypeptide (such as HNP-1) including at least one ornithine residue in place of an arginine residue are also disclosed.

Method for the treatment of pulmonary disease and method of producing proteins of use therein

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.

Growing community of inventors

Gaithersburg, MD, United States of America

Linda Stevens