Solubility and aggregation of commercial α-lactalbumin at neutral pH

McGuffey, Matthew K; Otter, Don; Zanten, John H. van; Foegeding, E. Allen

doi:10.1016/j.idairyj.2007.04.003

Cited by 29 publications

(12 citation statements)

References 55 publications

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“…Similarly, the aggregation behavior of two other commercial preparations (A and B) of α -La was found to be signifi cantly different at 95 ° C at neutral pH in a complex mineral salt environment. 282 Preparation A had a higher solubility at pH 6.75 and 6.8, yielded more reactive thiol groups, had a (25%) faster fi rst -order rate constant, and formed spherical aggregates with much higher -molecular -weight species than preparation B. 282 While preparation A showed much higher aggregation tendency at pH 4.6, preparation B aggregated signifi cantly more than preparation A at pH 6.75 and 6.8.…”

Section: Sources Of Proteinsmentioning

confidence: 99%

External Factors Affecting Protein Aggregation

Wang

Speaker

2010

Aggregation of Therapeutic Proteins

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The behavior of biotherapeutic proteins is signifi cantly different from small molecule drugs both in liquid and solid states, especially in terms of physical stability. One such property is the high tendency of protein molecules to aggregate under a variety of conditions. The aggregation tendency is arguably the most common and troubling manifestation of protein instability during the development of protein biotherapeutics. 1 Protein aggregates usually exhibit either reduced or, in many cases, no biological activity. 2 -5 A clear correlation was established between loss of recombinant factor VIII (rFVIII ) and its degree of aggregation as shown in Fig. 4.1 . 6 To achieve effective prevention or inhibition of protein aggregation, it is of paramount importance to understand all the possible factors that affect or control the protein aggregation process.Many factors have been identifi ed and reported in the literature affecting the process and rate of protein aggregation. These factors can be roughly divided into two major categories: internal (protein structure related) and external (protein environment related). Chapter 3 in this book has focused extensively on factors that belong to the fi rst category. This chapter focuses on the external factors that affect the process and rate of protein aggregation. To facilitate discussion, these external factors are further divided into the following sections: (1) temperature; (2) solution conditions and composition (pH, buffer type and concentration, ionic strength, excipients and level, protein concentration, metal ions, denaturing and reducing agents, impurities, organic solvents, containers/closures, sources of proteins, sample treatment, and analytical methodologies); (3) processing steps (fermentation/expression,

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Section: Sources Of Proteinsmentioning

confidence: 99%

External Factors Affecting Protein Aggregation

Wang

Speaker

2010

Aggregation of Therapeutic Proteins

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“…Proteins, owing to the special features of their molecular structure (a large number of both the polar and non-polar functional groups in their molecules), are prone to pronounced self-assembly in an aqueous medium as a result of weak physical bond formation, the character of which is varies markedly by the environmental conditions, such as acidification, addition of divalent ions or low-molecular mass ingredients, temperature or high-pressure treatment, fermentation (Semenova, 2007). In recent years, DLS has been used for studying the aggregation of b-lactoglobulin, a-lactalbumin, caseins and other proteins (Baeza, Gugliotta, & Pilosof, 2001;Elofsson, Dejmek, & Paulsson, 1996;Guyomarc'h, Nono, Nicolai, & Durand, 2009;Harnsilawat, Pongsawatmanit, & McClements, 2006;Hoffmann, Roefs, Verheul, Van Mil, & De Kruif, 1996;Karlsson, Ipsen, Schrader, & Ardö , 2005;McGuffey, Otterb, van Zantenc, & Foegeding, 2007;Mehalebi, Nicolai, & Durand, 2008;Roefs & De Kruif, 1994;Sharma, Haque, & Wilson, 1996). However, studies on CMP aggregation by this technique have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Casein glycomacropeptide pH-dependent self-assembly and cold gelation

Farı́as

Martínez

Pilosof

2010

International Dairy Journal

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“…In addition to the process‐related impurities, contaminants can be brought into the final DS preparations through any of the above processes. The difference in the type and level of impurities or contaminants in different protein preparations could explain the different extent and mechanism of degradation for recombinant human thrombopoietin (rhTPO), and different aggregation behaviors of three commercially holo‐α‐lactalbumin products—Sigmaα‐La, IEXα‐La, and Cα‐La, at different pHs …”

Section: Drug Substance Manufacturingmentioning

confidence: 99%

“…The difference in the type and level of impurities or contaminants in different protein preparations could explain the different extent and mechanism of degradation for recombinant human thrombopoietin (rhTPO), 34 and different aggregation behaviors of three commercially holo-"-lactalbumin products-Sigma"-La, IEX"-La, and C"-La, at different pHs. 43,44…”

Section: Drug Substance Manufacturingmentioning

confidence: 99%