Dehydration-induced conformational transitions in proteins and their inhibition by stabilizers

Biophys J. 1993 Aug;65(2):661-71. doi: 10.1016/S0006-3495(93)81120-2.

Abstract

Dehydration of proteins results in significant, measurable conformational changes as observed using Fourier-transform infrared spectroscopy and resolution-enhancement techniques. For several proteins these conformational changes are at least partially irreversible, since, upon rehydration, denaturation and aggregation are observed. The presence of certain stabilizers inhibited these dehydration-induced transitions; the native structure was preserved in the dried state and upon reconstitution. Conformational transitions were also observed in a model polypeptide, poly-L-lysine, after lyophilization and were inhibited with the addition of stabilizing cosolutes. The ability of a particular additive to preserve the aqueous structure of dehydrated proteins and poly-L-lysine upon dehydration correlates directly with its ability to preserve the activity of lactate dehydrogenase, a labile enzyme, during drying.

MeSH terms

  • Animals
  • Drug Stability
  • Enzyme Stability
  • Fibroblast Growth Factor 2 / chemistry
  • Freeze Drying
  • Granulocyte Colony-Stimulating Factor / chemistry
  • Humans
  • Interferon-gamma / chemistry
  • L-Lactate Dehydrogenase / chemistry
  • L-Lactate Dehydrogenase / metabolism
  • Polylysine / chemistry
  • Protein Conformation*
  • Proteins / chemistry*
  • Rabbits
  • Recombinant Proteins / chemistry
  • Spectrophotometry, Infrared
  • Sucrose

Substances

  • Proteins
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Granulocyte Colony-Stimulating Factor
  • Polylysine
  • Sucrose
  • Interferon-gamma
  • L-Lactate Dehydrogenase