Polymer conjugates of protegrin peptides
View Patent ↗The invention provides peptides that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the peptide not attached to the water-soluble oligomer.
1. A conjugate of formula:
wherein PRO is a protegrin moiety having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 and each mPEG has a weight average molecular weight in a range of from about 500 Daltons to about 100,000 Daltons.
2. The conjugate of claim 1 , wherein each mPEG has a weight-average molecular weight in a range of from about 500 Daltons to about 80,000 Daltons.
3. The conjugate of claim 1 , wherein each mPEG has a weight-average molecular weight in a range of from about 2000 Daltons to about 50,000 Daltons.
4. The conjugate of claim 1 , wherein each mPEG has a weight-average molecular weight in a range of from about 5000 Daltons to about 40,000 Daltons.
5. A pharmaceutical composition comprising a conjugate of claim 1 and a pharmaceutically acceptable excipient.
6. The conjugate of claim 1 , wherein the protegrin moiety has an amino acid sequence that is at least 95% identical to SEQ ID NO: 1.
7. The conjugate of claim 1 , wherein the protegrin moiety has the amino acid sequence of SEQ ID NO: 1.
8. A method for making a conjugate of claim 1 comprising contacting, under conjugation conditions, a protegrin moiety with a polymeric reagent bearing a functional group.
9. A method of treatment of a microbial infection comprising administering a conjugate of claim 1 to a subject in need thereof.