X-Message-Number: 24291 Date: Tue, 22 Jun 2004 21:15:56 -0700 (PDT) From: Doug Skrecky <> Subject: Keeping Drugs Stable Without Refrigeration A spoonful of sugar may help the medicine go down, but it may take only a thin coating of freeze-dried sugar to keep insulin, vaccines and other heat-sensitive, protein-based drugs working reliably even when stored at room temperature and above. Widespread availability of stable, room-temperature therapeutic proteins and vaccines would lower the cost and increase the convenience of these drugs, and could dramatically improve distribution in areas of developing nations where refrigeration may be limited. New measurements taken by National Institute of Standards and Technology (NIST) scientists and published in the June edition of Biophysical Journal show that rapidly solidified sugars preserve such proteins best when they suppress tiny, molecular motions lasting a nanosecond or less. NIST scientists Christopher Soles and Marcus Cicerone used instruments at the NIST Center for Neutron Research to help them view nanoscale molecular motions of sugar mixtures that were designed to encase proteins. They found a striking correlation between sugar mixtures that provide unusually good protein stabilization and a suppression of very fast motions in the sugars. Scientists have known for more than a decade that "glassy" sugars can preserve medicines by encasing the proteins in a protective coating. The NIST measurements show that tiny molecular "wiggling" that facilitates protein degradation occurs at time and length scales smaller than once thought to matter. They found that diluting sugars that become "glassy" at a relatively high temperature with the right amount of glycerol formed a stiffer material, further restricting the protein's movement. It's as though the sugar glove is now made of cement instead of cloth, says Cicerone Biophys J. 2004 Jun;86(6):3836-45 Fast dynamics and stabilization of proteins: binary glasses of trehalose and glycerol. Cicerone MT, Soles CL. Polymers Division, National Institute of Standards and Technology, Gaithersburg, Maryland. We present elastic and inelastic incoherent neutron scattering data from a series of trehalose glasses diluted with glycerol. A strong correlation with recently published protein stability data in the same series of glasses illustrates that the dynamics at Q >/= 0.71 A(-1) and omega > 200 MHz are important to stabilization of horseradish peroxidase and yeast alcohol dehydrogenase in these glasses. To the best of our knowledge, this is the first direct evidence that enzyme stability in a room temperature glass depends upon suppressing these short-length scale, high-frequency dynamics within the glass. We briefly discuss the coupling of protein motions to the local dynamics of the glass. Also, we show that T(g) alone is not a good indicator for the protein stability in this series of glasses; the glass that confers the maximum room-temperature stability does not have the highest T(g). Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=24291