Hydroxyapatite-targeting multiarm polymers and conjugates made therefrom

摘要

The present invention provides, among other things, polymeric reagents suitable for reaction with biologically active agents to form conjugates, the polymeric reagents comprising one or more polymer chains and a plurality of hydroxyapatite-targeting moieties, and optionally the reagents include one or more degradable linkages that serve to divide the polymer chains into polymer segments having a molecular weight suitable for renal clearance.

主权项

1. A polymer conjugate having the structure:wherein:
B is —(X3)d-(L3)e-(X4)f-POLY2-L4-Drug or —(X3)d-(L3)e-(X4)f-L4-Drug; each POLY1 and POLY2, which may be the same or different, is a water-soluble, non-peptidic polymer; each X1, X2, X3, and X4, which may be the same or different, is a spacer moiety; each L1, L2, L3, and L4 which may be the same or different, are linkages; Drug is a residue of a biologically active moiety; Z3 is L5-Drug wherein L5 is a linkage or Z3 is selected from a multiarm structure selected from the group consisting ofwherein each m is 1-350, Me is methyl, and each Z is a hydroxyapatite-targeting moiety with the proviso that at least one Z3 is a multiarm structure;
each a, b, c, d, e, and f, which may be the same or different, is either zero or one; R is a monomeric or oligomeric multiarm core molecule derived from a molecule comprising at least p+1 sites available for attachment; and p is an integer in the range of 2-32.