Amylin Conjugation with Methoxyl Polyethyleneglycol

Author(s): Mariana F. A. N. Guterres, Luiz Henrique Guerreiro, Bruno Melo-Ferreira, Luiza C. S. Erthal, Luís Maurício T. R. Lima.

Journal Name: Protein & Peptide Letters

Volume 20 , Issue 11 , 2013

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Abstract:

We modified amylin chemically by conjugating methoxyl polyethyleneglycol succinimidyl carbonate (mPEGSC) of varying molecular weights (1 kDa, 2 kDa and 5 kDa). The reaction occurred within a few minutes, resulting in at least four distinct PEGylated products. The reaction products were separated by reversed-phase chromatography and identified by mass-spectrometry. The monoPEGylated and diPEGylated amylin products were generated rapidly through conjugation to the two amino groups of the N-terminal lysine residue. Both PEGylated amylin products bound to the receptor activity-modifying protein 1 (RAMP1). Pharmacological evaluation by subcutaneous administration in mice of monoPEGylated and diPEGylated amylin obtained with mPEG-SC 5 kDa revealed that both compounds modulated glycemia for longer times than unmodified amylin. Collectively, these data demonstrate the potential of bioconjugation with mPEG for the design of amylin therapeutics with sustained action.

Keywords: Amylin, diabetes, glycemia, islet associated polypeptide, PEGylation.

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Article Details

VOLUME: 20
ISSUE: 11
Year: 2013
Page: [1264 - 1271]
Pages: 8
DOI: 10.2174/09298665113209990067
Price: $65

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