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Second virial coefficient determination of a therapeutic peptide by self‐interaction chromatography
Author(s) -
Payne Robert W.,
Nayar Rajiv,
Tarantino Ralph,
Terzo Sam Del,
Moschera John,
Di Jie,
Heilman David,
Bray Brian,
Manning Mark Cornell,
Henry Charles S.
Publication year - 2006
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20554
Subject(s) - virial coefficient , chemistry , peptide , solubility , salt (chemistry) , chromatography , static light scattering , macromolecule , crystallization , aqueous solution , partition coefficient , virial expansion , dynamic light scattering , organic chemistry , thermodynamics , chemical engineering , biochemistry , physics , nanoparticle , engineering
Self‐interaction of macromolecules has been shown to play an important role in a number of physical processes, including crystallization, solubility, viscosity, and aggregation. Peptide self‐interaction is not as well studied as for larger proteins, but should play an equally important role. The osmotic second virial coefficient, B , can be used to quantify peptide and protein self‐interaction. B values are typically measured using static light scattering (SLS). Peptides, however, do not scatter enough light to allow such measurements. This study describes the first use of self‐interaction chromatography (SIC) for the measurement of peptide B values because SIC does not have the molecular size limitations of SLS. In the present work, SIC was used to measure B for enfuvirtide, a 36‐amino acid therapeutic peptide, as a function of salt concentration, salt type, and pH. B was found to correlate strongly with solubility and apparent molecular weight. In general, the solubility of enfuvirtide increases with pH from 6 to 10 and decreases as the salt concentration increases from 0 to 0.5 M for three different salts. The effect of peptide concentration on B was also investigated and shown to have a significant effect, but only at high concentrations (>80 mg/mL). © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 527–533, 2006