N-maleimidyl polymer derivatives
The invention is directed to multi-functional N-maleimidyl polymer derivatives comprising a water soluble and non-peptidic polymer backbone having a terminal carbon, such as a poly(alkylene glycol), the terminal carbon of the polymer backbone being directly bonded to the nitrogen atom of a N-maleimidyl moiety without a linking group therebetween. The invention also provides two methods of preparing such linkerless N-maleimidyl polymer derivatives.
1. A heterobifunctional N-maleimidyl poly(ethylene glycol) derivative having the formula:
wherein:
X is amine (—NH 2 ) or protected amine; and
n is about 20 to about 4000.
2. The heterobifunctional N-maleimidyl poly(ethylene glycol) derivative of claim 1 , wherein X is a protected amine.
3. The heterobifunctional N-maleimidyl poly(ethylene glycol) derivative of claim 2 , wherein the protected amine comprises a protecting group that is either tert-butyloxycarbonyl (t-Boc) or 9-fluorenylmethoxycarbonyl (Fmoc).
4. The heterobifunctional N-maleimidyl poly(ethylene glycol) derivative of claim 3 , wherein the protected amine comprises a tert-butyloxycarbonyl (t-Boc) protecting group.
5. The heterobifunctional N-maleimidyl poly(ethylene glycol) derivative of claim 3 , wherein the protected amine comprises a 9-fluorenylmethoxycarbonyl (Fmoc) protecting group.
6. The heterobifunctional N-maleimidyl poly(ethylene glycol) derivative of claim 1 , wherein n is about 20 to about 2000.
7. The heterobifunctional N-maleimidyl poly(ethylene glycol) derivative of claim 1 , having a molecular weight of from around 6,000 daltons to about 80,000 daltons.
8. The heterobifunctional N-maleimidyl poly(ethylene glycol) derivative of claim 1 in purified form.