Branched polyalkylene glycols

1. A branched polyalkylene glycol represented by formula (I):

(R 1 —M n —X 1 ) m L(X 2 —X 3 —R 2 ) q   (I)

{wherein L is

M represents OCH 2 CH 2 , OCH 2 CH 2 CH 2 , OCH(CH 3 )CH 2 , (OCH 2 CH 2 ) r —(OCH 2 CH 2 CH 2 ) s (in which r and s, which may be the same or different, each represent an arbitrary positive integer) or (OCH 2 CH 2 ) ra —[OCH(CH 3 )CH 2 ] sa (in which ra and sa have the same meanings as the above r and s, respectively);

n represents an arbitrary positive integer;

m represents an integer of 3 or more;

q represents an integer of 1 to 3;

R 1 represents a hydrogen atom, lower alkyl or lower alkanoyl;

R 2 represents a group having reactivity with an amino acid side chain, the N-terminal amino group or the C-terminal carboxyl group in a polypeptide or a group convertible into the group having reactivity;

X 1 represents R 4 —NH—C(═O)—R 5 [in which R 4 represents a bond, alkylene or O(CH 2 ) tc (in which tc represents an integer of 1 to 8) and R 5 represents a bond;

X 2 represents a bond, O or (CH 2 ) te O (in which te has the same meaning as the above tc);

X 3 represents a bond or alkylene; and

three or more R 1 —M n —X 1 's may be the same or different, and when two or three X 2 —X 3 —R 2 's are present (when q is 2 or 3), they may be the same or different}.

2. The branched polyalkylene glycol according to claim 1 , wherein q is 1.

3. The branched polyalkylene glycol according to claim 1 , wherein m is 3 or 4.

4. The branched polyalkylene glycol according to any of claims 1 to 3 , wherein n is 10 to 100,000, and r and s, and ra and sa, which may be the same or different, each represent 1 to 100,000.

5. The branched polyalkylene glycol according to claim 4 , wherein R 2 is a hydroxyl group, carboxy, formyl, amino, vinylsulfonyl, mercapto, cyano, carbamoyl, halogenated carbonyl, halogenated lower alkyl, isocyanato, isothiocyanato, oxiranyl, lower alkanoyloxy, maleimido, succinimidooxycarbonyl, substituted or unsubstituted aryloxycarbonyl, benzotriazolyloxycarbonyl, phthalimidooxycarbonyl, imidazolylcarbonyl, substituted or unsubstituted lower alkoxycarbonyloxy, substituted or unsubstituted aryloxycarbonyloxy, tresyl, lower alkanoyloxycarbonyl, substituted or unsubstituted aroyloxycarbonyl, substituted or unsubstituted aryldisulfido, or azido.

6. The branched polyalkylene glycol according to claim 5 , which has a molecular weight of 500 to 1,000,000.

7. A chemically modified polypeptide wherein a physiologically active polypeptide or its derivative is modified with at least one branched polyalkylene glycol according to claim 6 directly or through a spacer.

8. The chemically modified polypeptide according to claim 7 , wherein the physiologically active polypeptide is an enzyme, a cytokine or a hormone.

9. A pharmaceutical composition comprising the chemically modified polypeptide according to claim 8 and a pharmaceutically acceptable carrier.

10. The branched polyalkylene glycol according to claim 2 , wherein n is 10 to 100,000, and r and s, and ra and sa, which may be the same or different, each represent 1 to 100,000.

11. The branched polyalkylene glycol according to claim 3 , wherein n is 10 to 100,000, and r and s, and ra and sa, which may be the same or different, each represent 1 to 100,000.

12. The branched polyalkylene glycol according to claim 10 , wherein R 2 is a hydroxyl group, carboxy, formyl, amino, vinylsulfonyl, mercapto, cyano, carbamoyl, halogenated carbonyl, halogenated lower alkyl, isocyanato, isothiocyanato, oxiranyl, lower alkanoyloxy, maleimido, succinimidooxycarbonyl, substituted or unsubstituted aryloxycarbonyl, benzotriazolyloxycarbonyl, phthalimidooxycarbonyl, imidazolylcarbonyl, substituted or unsubstituted lower alkoxycarbonyloxy, substituted or unsubstituted aryloxycarbonyloxy, tresyl, lower alkanoyloxycarbonyl, substituted or unsubstituted aroyloxycarbonyl, substituted or unsubstituted aryldisulfido, or azido.

13. The branched polyalkylene glycol according to claim 11 , wherein R 2 is a hydroxyl group, carboxy, formyl, amino, vinylsulfonyl, mercapto, cyano, carbamoyl, halogenated carbonyl, halogenated lower alkyl, isocyanato, isothiocyanato, oxiranyl, lower alkanoyloxy, maleimido, succinimidooxycarbonyl, substituted or unsubstituted aryloxycarbonyl, benzotriazolyloxycarbonyl, phthalimidooxycarbonyl, imidazolylcarbonyl, substituted or unsubstituted lower alkoxycarbonyloxy, substituted or unsubstituted aryloxycarbonyloxy, tresyl, lower alkanoyloxycarbonyl, substituted or unsubstituted aroyloxycarbonyl, substituted or unsubstituted aryldisulfido, or azido.

14. The branched polyalkylene glycol according to claim 12 , which has a molecular weight of 500 to 1,000,000.

15. The branched polyalkylene glycol according to claim 13 , which has a molecular weight of 500 to 1,000,000.