A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams.

A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. Research Abstract Details 

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A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. Abstract Text:

AC137 (pramlintide) is a 37-residue peptide analogue of the hormone amylin. Pramlintide has been studied as an adjunct antihyperglycemic treatment for patients with type 2 or type 1 diabetes who use insulin. This study took an empirical phase diagram (EPD) approach to obtain information about the structural stability of this peptide by compiling thermal perturbation data acquired from multiple spectroscopic methods, including high-resolution second-derivative UV absorbance spectroscopy, optical density, fluorescence, and circular dichroism. This approach enabled us to accomplish two major goals: (1) characterize the structure and physical stability of AC137 and (2) assess the application of EPDs to a small peptide. Results obtained at low concentration of AC137 revealed a peptide with ill-defined structure and insensitivity to pH. Use of isotope exchange NMR confirmed this lack of structure. At the current formulation of pH 4, AC137 exhibited stability at concentrations of 1.8 to 8.8 mg/mL. High concentrations of the peptide showed a tendency to aggregate at pH 6-7.5. Construction of EPDs under the various experimental conditions examined manifested color changes that correlated well with the raw data. The utility and limitations of the EPD approach when applied to weakly structured peptides are discussed. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2552-2567, 2008.

A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. Publishing Authors By Initials

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A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of pharmaceutical sciences

VOLUME: 97

Page Numbers: 2552-67

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ISSN: 0022-3549

DAY: 4

MONTH: Jul

YEAR: 2008

A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. Information

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LANGUAGE: eng

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Grant and Affiliation Information for A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams.

AFFILIATION: Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Drive (MRB 306), Lawrence, Kansas 66047.

Country: United States

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MEDLINETA: J Pharm Sci

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