N-terminally chemically modified protein compositions and methods

Abstract

Provided herein are methods and compositions relating to the attachment of water soluble polymers to proteins. Provided are novel methods for N-terminally modifying proteins or analogs thereof, and resultant compositions, including novel N-terminally chemically modified G-CSF compositions and related methods of preparation. Also provided is chemically modified consensus interferon.

1 - 11 . (canceled) 
     
     
         12 . A method for attaching a water soluble polymer to a protein or analog thereof, wherein said water soluble polymer has a single reactive aldehyde group, said method comprising:
 (a) reacting a protein moiety with a water soluble polymer moiety under reducing alkylation conditions, at a pH sufficiently acidic to selectively activate the α-amino group at the amino terminus of said protein moiety so that said water soluble polymer selectively attaches to said α-amino group; and   (b) obtaining the reaction product and   (c) optionally, separating the reaction products from unreacted moieties.   
     
     
         13 . A method of  claim 12  wherein said polymer is pharmaceutically acceptable. 
     
     
         14 . A method of  claim 12  wherein said water soluble polymer is selected from the group consisting of dextran, poly (n-vinyl pyurrolidone), polyethylene glycols, propropylene glycol homopolymers, prolypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols and polyvinyl alcohols. 
     
     
         15 . A method of  claim 14  wherein said polymer is polyethylene glycol. 
     
     
         16 . A method of  claim 12  wherein said reducing alkylation reaction involves the use of a reducing agent selected from sodium borohydride, sodium cyanoborohydride, dimethylamine borate, timethylamine borate and pyridine borate. 
     
     
         17 - 38 . (canceled)