CO 059: NOVEL PEGYLATION TECHNOLOGIES FOR THE DEVELOPMENT OF NEXT GENERATION BIODRUGS

J Pharm Pharmacogn Res 2(Suppl. 1): S36, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 059: NOVEL PEGYLATION TECHNOLOGIES FOR THE DEVELOPMENT OF NEXT GENERATION BIODRUGS

Ikeda Y1, Katamachi J1, Kawasaki H1, Nagasaki Y2.

1Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan
2 Master’s School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan. E-mail: ikeda@ims.tsukuba.ac.jp
3Satellite Laboratory, International Center for Materials Nanoarchitectonics (MANA), National Institute of Materials Science (NIMS), Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
Abstract

Introduction: PEGylation refers to the covalent attachment of poly(ethylene glycol) on the biomolecules. PEGylation is recognized as a promising method to increase the therapeutic efficacy of medicines in clinical settings. A variety of molecules have been modified with PEG and several PEGylated drugs have been approved in clinical settings. In this presentation, our recent developments of novel PEGylation technologies on biomolecules will be shown.

Material and methods: For the construction of PEGylated oligonucleotide by solid phase synthesis, a novel solid phase which was pre-installed with PEG was prepared. In the case of protein PEGylation, a novel PEG derivative which possesses glutaraldehyde at one end has been synthesized.

Results: Solid phase synthesis of PEGylated oligonucleotide. A novel solid-phase synthesis method for poly(ethylene glycol) (PEG)oligonucleotide conjugates was developed to increase the stability of therapeutic oligonucleotides such as antisense oligonucleotides and siRNA. A prepared solid phase was pre-installed with PEG to provide oligonucleotides modified with PEG at the 3′ terminus. Compared with the conventional liquid-phase synthesis method, the developed solid-phase method is simple and reproducible. PEGylation at the 3′ terminus was confirmed to stabilize not only DNA but also RNA more than PEGylation at the 5′ terminus, which has been widely used thus far. A novel chemistry for the PEGylated protein with a high activity. Several PEGylated proteins have been approved as therapeutic drugs. In many cases, PEGylated protein has been synthesized by the conjugation reaction between PEG possessing activated ester and amine(s) in the protein. This reaction, however, often causes inactivation of PEGylated proteins.

Conclusions: In this report, we present a novel chemistry which enables the PEGylation of proteins under the mild reaction condition. PEGylated protein prepared by the method developed exhibited much higher biological activity than the PEGylated protein prepared by the conventional method.