Compatible solutes are best described as organic osmolytes responsible
for osmotic balance and at the same time compatible with the cells' m
etabolism. A comprehensive survey (using HPLC and NMR methods) on halo
philic/halotolerant eubacteria has revealed the full diversity of comp
atible solutes employed in nature. Molecular principles derived from t
he spectrum of compounds found in the bacterial world may be summarize
d as follows. Compatible solutes are polar, highly soluble molecules a
nd uncharged at physiological pH. With the exception of proline (a pro
teinogenic amino acid) they are characterized as amino acid derivative
s of the following types: betaines, ectoines, N-acetylated diamino aci
ds and N-derivatized carboxamides of glutamine. Using near-infrared sp
ectroscopy we have also been able to demonstrate that compatible solut
es are strong water-structure formers and as such probably excluded fr
om the hydration shell of proteins. This ''preferential exclusion'' pr
obably explains their function as effective stabilizers of the hydrati
on shell of native proteins (protection against heating freezing and d
rying). Hence these typical products of halophilic eubacteria have a c
onsiderable potential as stabilizing/protecting agents on both molecul
ar and whole-cell level. Thorough understanding of common structural p
rinciples and fundamental water-solute interactions will ultimately en
able us to design novel highly efficient stress protectants and stabil
izers of biomolecules.