The United States of America; as represented by the Secretary; Department of Health and Human Serv
发明人:
Joel Moss,Linda Stevens,Rodney L. Levine
申请号:
US14450512
公开号:
US20140341876A1
申请日:
2014.08.04
申请国别(地区):
US
年份:
2014
代理人:
摘要:
Methods of treating a subject with pulmonary disease by administering a therapeutically effective amount of a defensin polypeptide including at least one arginine residue susceptible to ADP-ribosylation and nicotinamide adenine dinucleotide (NAD), are described. The polypeptide and/or NAD can be administered via inhalation. Also disclosed is a pharmaceutical composition including at least one defensin polypeptide and NAD. In vitro methods of producing a polypeptide with altered activity, including contacting the polypeptide with NAD and an arginine-specific mono-ADP-ribosyltransferase 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, are also described. Methods of treating a subject with pulmonary disease by administering a therapeutically effective amount of a modified defensin polypeptide including at least one ornithine residue in place of an arginine residue are also disclosed.