Conformational stability and self-association equilibrium in biologics.
Drug Discovery Today(2016)
Abstract
Biologics exist in equilibrium between different conformational states (native, partially denatured or fully denatured states). Any of these conformations may have a propensity to aggregate. An important goal in the development of protein therapeutics is to identify the protein variants and/or the formulations that optimize the stability/aggregation profile. Since conformational stability and self-association are thermodynamically linked functions, the concentration dependence of conformational stability reveal aggregation tendencies at very early stages and provide critical information for accelerated development.
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Key words
Biologics,Conformational equilibrium,Differential scanning calorimetry,Isothermal chemical denaturation,Protein aggregation
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