Polyethylene glycol derivatives, modified peptides and production thereof

• US 5,214,131 A
• Filed: 11/26/1991
• Issued: 05/25/1993
• Est. Priority Date: 05/06/1988
• Status: Expired due to Fees

• Current Assignee: Sumitomo Pharmaceuticals Company Limited (Sumitomo Chemical Company Limited)
• Original Assignee: Sumitomo Pharmaceuticals Company Limited (Sumitomo Chemical Company Limited)
• Inventors: Sano, Akihiko, Maeda, Hiroo, Ono, Keiichi, Kai, Yoshiyuki
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Celsa, Bennett M.
• Application Number:
  US07/798,138
• Time in Patent Office: 546 Days
• Field of Search: 530/345, 530/402, 530/406, 530/409, 568/308, 568/335, 568/337, 526/313, 526/316
• US Class Current: 530/345
• CPC Class Codes: C07K 1/064 for omega-amino or -guanidino functions
• CPC Class Codes: C07K 1/1077 by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
• CPC Class Codes: C08G 65/323 containing halogens
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/3346 having sulfur bound to carbon and oxygen

Abstract

A polyethylene glycol derivative of the formula ##STR1## wherein R represents a lower alkyl and n represents an optional positive integer which renders the average molecular weight of the polyethylene glycol moiety about 1,000 to 12,000, a peptide modified by said polyethylene glycol derivative and a method for production thereof. The polyethylene glycol derivative (I) is capable of modifying the guanidino groups in peptides. The peptides modified by the polyethylene glycol derivative (I) are extremely stable, are considerably delayed in biological clearance (i.e. the durability is extended) and exhibit their physiological activities effectively over the long period.

Claims

1. A modified peptide in which the guanidino group is modified by covalently attaching a polyethylene glycol derivative of the formula ##STR10## wherein R represents a lower alkyl and n represents a positive integer which renders the average molecular weight of the polyethylene glycol moiety about 1,000 to 12,000 daltons.

2. A modified peptide as claimed in claim 1 which is selected from the group consisting of plasminogen activators modified by 4-monomethoxypolyethylene glycol-phenylglyoxal, growth hormone-releasing factors modified by 4-monomethoxypolyethylene glycol-phenylglyoxal, granulocyte macrophage colony-stimulating factors modified by 4-monomethoxypolyethylene glycol-phenylglyoxal, superoxide dismutases modified by 4-monomethoxypolyethylene glycol-phenylglyoxal and insulin-like growth factors modified by 4-monomethoxy-polyethylene glycol-phenylglyoxal.