New Method for the Synthesis and Purification of Branched mPEG2lys

MARIANELA GONZÁLEZ, RICARDO J. A. GRAU, SANTIAGO E. VAILLARD

REACTIVE & FUNCTIONAL POLYMERS

ELSEVIER SCIENCE BV

Lugar: Oxford; Año: 2012 vol. 12 p. 107 - 113

1381-5148

Branched PEG structures are particularly useful for the pegylation of different biomaterials. In this regard, the branched structure bearing a lysine core and two mPEG chains linked by urethane bonds (mPEG2lys) has been used for the pegylation of several important biomolecules. In this work we describe the preparation of a new functionalized mPEG featuring an alkoxy-carbonylimidazolium iodide reactive group that can be used for the urethane bonds formation required in mPEG2lys (20 kDa). The procedure for the preparation of the mPEG-alkoxy-carbonylimidazolium iodide involves the initial reaction of mPEG with N,N´-carbonylbismidazole (CDI) as phosgene equivalent, followed by alkylation with methyl iodide. The functionalized mPEG was reacted with a silylated lysine derivative affording mPEG2lys in a single step. Therefore, harmful reagents (like phosgene derivatives) are not employed, making the process safe and straightforward. A 2-step purification procedure of mPEG2lys is also presented. It is noteworthy that by following this method pure mPEG2lys was obtained with 41% isolated yield. The mPEG2lys was further converted to the N-hydroxysuccinimidyl ester by diimide activation and successfully used in the pegylation of interferon a-2a.