title: Dehydration-induced conformational transitions in proteins and their inhibition by stabilizers.
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.
authors.affiliation: Department of Protein Chemistry, Amgen, Inc., Thousand Oaks, California 91320.
authors.forename: S J
authors.initials: SJ
authors.lastname: Prestrelski
authors.forename: N
authors.initials: N
authors.lastname: Tedeschi
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
authors.forename: J F
authors.initials: JF
authors.lastname: Carpenter
mesh_terms: D000818:Animals; D004355:Drug Stability; D004795:Enzyme Stability; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry; D005612:Freeze Drying; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013395:Sucrose
chemical_list: D011506:Proteins; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor; D011107:Polylysine; D013395:Sucrose; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase