Asparagine deamidation in recombinant human lymphotoxin: Hindrance by three-dimensional structures

Stability of Protein Pharmaceuticals: An Update

“…In 1988, Kossiakoff demonstrated that polypeptide chain flexibility impacted deamidation rates (30). Other studies have since arrived at the same conclusions, examining the relative deamidation rates for Asn residues dispersed across a given globular protein structure (31,32). In addition, a number of studies have shown that placement of the reactive Asn residue within an ordered secondary structure slows the reaction rate.…”

The Complex Inter-Relationships Between Protein Flexibility and Stability

“…Many studies have looked at the effect of conformation and structure on the chemical degradation rates of model peptides, and this has strongly shaped our current understanding of these processes. [158][159][160][161][162][163][164][165][166][167][168][169][170][171][172] It is necessary, however, to further probe the finer details of the relationships between chemical degradation and protein dynamics using varying timescales and the idea that proteins are statistical distributions of conformational microstates with varying degrees of flexibility.…”

“…responsible for stabilization of a particular Asn residue by prevention of the adoption of a conformation necessary for cyclic amide formation and subsequent deamidation. 196 Many more examples exist in which the rates of deamidation depend on a proteins sequence, structure and/or structural flexibility. 165,172,[190][191][192][193][194]197 Our understanding of deamidation may be enhanced by reviewing previous studies of natural biological mechanisms that increase deamidation of certain residues in a functional manner.…”

Formulation and Immunogenicity of a Potential Multivalent Type III Secretion System-Based Protein Vaccine

“…There is mounting evidence that proteins are in general more chemically stable when a high degree of secondary and tertiary structure exists. [42][43][44][45][46][47][48] Indeed, even the deamidation in BipD does not refute this explanation. Since the Asn residue is second in the primary sequence, it may not be part of any rigid structural feature that would inhibit the formation of the critical cyclic-imide intermediate.…”