{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:54:51Z","timestamp":1791424491755,"version":"4.3.3"},"reference-count":0,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[1998,8,1]],"date-time":"1998-08-01T00:00:00Z","timestamp":901929600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Quart. Rev. Biophys."],"published-print":{"date-parts":[[1998,8]]},"abstract":"<jats:p>Alcohol based cosolvents, such as trifluoroethanol (TFE) have been used for \nmany decades to denature proteins and to stabilize structures in peptides. \nNuclear magnetic resonance spectroscopy and site directed mutagenesis have \nrecently made it possible to characterize the effects of TFE and of other \nalcohols on polypeptide structure and dynamics at high resolution. This review \nexamines such studies, particularly of hen lysozyme and \u03b2-lactoglobulin. It \npresents an overview of what has been learnt about conformational preferences \nof the polypeptide chain, the interactions that stabilize structures and the \nnature of the denatured states. The effect of TFE on transition states and on \nthe pathways of protein folding and unfolding are also reviewed. Despite \nconsiderable progress there is as yet no single mechanism that accounts for all \nof the effects TFE and related cosolvents have on polypeptide conformation. \nHowever, a number of critical questions are beginning to be answered. Studies \nwith alcohols such as TFE, and \u2018cosolvent engineering\u2019 in general, have \nbecome valuable tools for probing biomolecular structure, function and \ndynamics.<\/jats:p>\n                  <jats:p>1. COSOLVENTS: OLD HAT? 298<\/jats:p>\n                  <jats:p>2. HOW DOES TFE WORK? 299<\/jats:p>\n                  <jats:p>\n                    2.1\n                    <jats:italic>Effect on hydrogen bonding<\/jats:italic>\n                    300\n                  <\/jats:p>\n                  <jats:p>\n                    2.2\n                    <jats:italic>Effect on non-polar sidechains<\/jats:italic>\n                    301\n                  <\/jats:p>\n                  <jats:p>\n                    2.3\n                    <jats:italic>Effect on solvent structure<\/jats:italic>\n                    302\n                  <\/jats:p>\n                  <jats:p>3. EFFECTS OF TFE ON (UN-)FOLDING TRANSITIONS 303<\/jats:p>\n                  <jats:p>\n                    3.1\n                    <jats:italic>Pretransition<\/jats:italic>\n                    303\n                  <\/jats:p>\n                  <jats:p>\n                    3.2\n                    <jats:italic>Transition<\/jats:italic>\n                    304\n                  <\/jats:p>\n                  <jats:p>\n                    3.3\n                    <jats:italic>Posttransition<\/jats:italic>\n                    305\n                  <\/jats:p>\n                  <jats:p>\n                    3.4\n                    <jats:italic>Far UV CD spectroscopic detection of structure<\/jats:italic>\n                    306\n                  <\/jats:p>\n                  <jats:p>\n                    3.5\n                    <jats:italic>Effect with temperature<\/jats:italic>\n                    306\n                  <\/jats:p>\n                  <jats:p>\n                    3.6\n                    <jats:italic>Effect with additional denaturants<\/jats:italic>\n                    306\n                  <\/jats:p>\n                  <jats:p>4. THERMODYNAMIC PARAMETERS FROM STRUCTURAL TRANSITIONS OF PEPTIDES AND PROTEINS IN TFE 307<\/jats:p>\n                  <jats:p>5. ADVANCES IN NMR SPECTROSCOPY 310<\/jats:p>\n                  <jats:p>\n                    5.1\n                    <jats:italic>Chemical shifts<\/jats:italic>\n                    310\n                  <\/jats:p>\n                  <jats:p>\n                    5.2\n                    <jats:sup>3<\/jats:sup>\n                    <jats:italic>[Jscr    ]<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>HNH\u03b1<\/jats:italic>\n                    <\/jats:sub>\n                    <jats:italic>coupling constants<\/jats:italic>\n                    311\n                  <\/jats:p>\n                  <jats:p>\n                    5.3\n                    <jats:italic>Amide hydrogen exchange<\/jats:italic>\n                    312\n                  <\/jats:p>\n                  <jats:p>\n                    5.4\n                    <jats:italic>Nuclear Overhauser Effects<\/jats:italic>\n                    (\n                    <jats:italic>NOEs<\/jats:italic>\n                    ) 312\n                  <\/jats:p>\n                  <jats:p>6. \u03b1-HELIX \u2013 EVERYWHERE? 313<\/jats:p>\n                  <jats:p>\n                    6.1\n                    <jats:italic>Intrinsic helix propensity equals helix content?<\/jats:italic>\n                    313\n                  <\/jats:p>\n                  <jats:p>\n                    6.2\n                    <jats:italic>A helix propensity scale for the amino acids in TFE<\/jats:italic>\n                    314\n                  <\/jats:p>\n                  <jats:p>\n                    6.3\n                    <jats:italic>Capping motifs and stop signals<\/jats:italic>\n                    315\n                  <\/jats:p>\n                  <jats:p>\n                    6.4\n                    <jats:italic>Limits and population of helices as seen by CD and NMR<\/jats:italic>\n                    316\n                  <\/jats:p>\n                  <jats:p>7. TURNS 317<\/jats:p>\n                  <jats:p>8. \u03b2-HAIRPINS AND SHEETS 317<\/jats:p>\n                  <jats:p>9. \u2018CLUSTERS\u2019 OF SIDECHAINS 320<\/jats:p>\n                  <jats:p>10. THE TFE DENATURED STATE OF \u03b2-LACTOGLOBULIN 321<\/jats:p>\n                  <jats:p>11. THE TFE DENATURED STATE OF HEN LYSOZYME 324<\/jats:p>\n                  <jats:p>12. TERTIARY STRUCTURE, DISULPHIDES, DYNAMICS AND COMPACTNESS 327<\/jats:p>\n                  <jats:p>13. PROSPECTS FOR STRUCTURE CALCULATION 328<\/jats:p>\n                  <jats:p>14. EFFECT OF TFE ON QUATERNARY STRUCTURE 329<\/jats:p>\n                  <jats:p>15. EFFECT ON TFE ON UN- AND REFOLDING KINETICS 330<\/jats:p>\n                  <jats:p>16. OTHER USES 336<\/jats:p>\n                  <jats:p>\n                    16.1\n                    <jats:italic>Mimicking membranes and protein receptors<\/jats:italic>\n                    336\n                  <\/jats:p>\n                  <jats:p>\n                    16.2\n                    <jats:italic>Solubilizing peptides and proteins<\/jats:italic>\n                    336\n                  <\/jats:p>\n                  <jats:p>\n                    16.3\n                    <jats:italic>Cosolvents as helpers for protein folding?<\/jats:italic>\n                    338\n                  <\/jats:p>\n                  <jats:p>\n                    16.4\n                    <jats:italic>Modifying protein dynamics and catalysis<\/jats:italic>\n                    338\n                  <\/jats:p>\n                  <jats:p>\n                    16.5\n                    <jats:italic>Effects on nucleic acids<\/jats:italic>\n                    339\n                  <\/jats:p>\n                  <jats:p>\n                    16.6\n                    <jats:italic>Effects on lipid bilayers and micelles<\/jats:italic>\n                    339\n                  <\/jats:p>\n                  <jats:p>\n                    16.7\n                    <jats:italic>Future applications<\/jats:italic>\n                    339\n                  <\/jats:p>\n                  <jats:p>17. CONCLUSIONS: TFE \u2013 WHAT IS IT GOOD FOR? 340<\/jats:p>\n                  <jats:p>18. ACKNOWLEDGMENTS 340<\/jats:p>\n                  <jats:p>19. REFERENCES 340<\/jats:p>","DOI":"10.1017\/s003358359800345x","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:36:03Z","timestamp":1027762563000},"page":"297-355","source":"Crossref","is-referenced-by-count":776,"title":["Trifluoroethanol and colleagues: cosolvents \ncome of age. Recent studies with peptides and proteins"],"prefix":"10.1017","volume":"31","author":[{"given":"MATTHIAS","family":"BUCK","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[1998,8,1]]},"container-title":["Quarterly Reviews of Biophysics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S003358359800345X","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T15:16:50Z","timestamp":1553872610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S003358359800345X\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,8]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1998,8]]}},"alternative-id":["S003358359800345X"],"URL":"https:\/\/doi.org\/10.1017\/s003358359800345x","relation":{},"ISSN":["0033-5835","1469-8994"],"issn-type":[{"value":"0033-5835","type":"print"},{"value":"1469-8994","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,8]]}}}