Franz Hofmeister
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'''Franz Hofmeister''' (1850-1922) was an early protein scientist, and is famous for his studies of salts that influence the solubility and conformational stability of [[protein]]s. Hofmeister was the first to propose that polypeptides were [[amino acid]]s linked by [[peptide bond]]s in 1902, although this model of protein [[primary structure]] was independently and simultaneously conceived by [[Emil Fischer]].
==Early life==
Hofmeister's father was a doctor in Prague, where Hofmeister first began his studies, under the physiologist Hugo Huppert, himself a student of Carl Lehmann. Hofmeister's ''Habilitationsschrift'' in 1879 concerned the peptic products of digestion.
Hofmeister became professor of Pharmacology in Prague in 1885, then moved to Strassbourg in 1896.
==The Hofmeister series==
{{main|Hofmeister series}}
Hofmeister discovered a series of salts that have consistent effects on the solubility of proteins and (it was discovered later) on the stability of their [[secondary structure|secondary]] and [[tertiary structure]]. Anions appear to have a larger effect than cations, and are usually ordered
:<math>
\mathrm{F^{-} \approx SO_{4}^{2-} > HPO_{4}^{2-} > acetate > Cl^{-} > NO_{3}^{-} > Br^{-} > ClO_{3}^{-} > I^{-} > ClO_{4}^{-} > SCN^{-}}
</math>
(This is a partial listing; many more salts have been studied.)
The order of cations is usually given as
:<math>
\mathrm{NH_{4}^{+} > K^{+} > Na^{+} > Li^{+} > Mg^{2+} > Ca^{2+} > guanidinium}
</math>
The mechanism of the Hofmeister series is not entirely clear, but seems to result mainly from effects on the solvent at higher salt concentrations (>100 mM). Early members of the series increase solvent surface tension and decrease the solubility of nonpolar molecules ("salt out"); in effect, they ''strengthen'' the [[hydrophobic interaction]]. By contrast, later salts in the series increase the solubility of nonpolar molecules ("salt in") and decrease the order in water; in effect, they ''weaken'' the [[hydrophobic effect]]. However, these salts also interact directly with proteins (which are charged and have strong dipole moments) and may even bind specifically (e.g., phosphate and sulfate binding to [[ribonuclease A]]). Ions that have a strong 'salting in' effect such as I<sup>-</sup> and SCN<sup>-</sup> are strong denaturants, because they salt in the peptide group, and thus interact much more strongly with the unfolded form of a protein than with its native form. Consequently, they 'pull' the unfolding reaction.<ref name="baldwin">{{cite journal |author=Baldwin RL. |title=How Hofmeister ion interactions affect protein stability |journal=Biophys J |volume=71 |issue=4 |pages=2056–63 |year=1996 |pmid=8889180}}</ref> Moreover, they may have direct interactions with some standard hydrophobic molecules, e.g., [[benzene]].
==Protein purification==
The importance of the Hofmeister series to early protein work cannot be underestimated, since it provided the chief tool for purifying proteins (sulfate precipitation) over the next ~50 years, one that is still in use today. Hofmeister himself may have been the first to crystallize a protein, hen egg-white albumin. Repeated crystallization was a favorite purification technique in the early days of protein science, and was essential for its development.
==Proposal of protein primary structure==
Hofmeister argued for peptide bonds by process of elimination. C-C, ether and ester bonds were unlikely considering the digestion by [[trypsin]]. =C-N-C= bonds could be eliminated because it would imply a much larger number of [[carboxylate]] groups than is observed experimentally.
Hofmeister also argued for peptide bonds based on the [[biuret reaction]] observed with all proteins but never with free amino acids. Since [[biuret]] has the formula NH2-CO-NH-CO-NH2, that suggested the presence of similar peptide bonds in proteins.
==See also==
* [[primary structure]]
* [[peptide bond]]
==References==
<references/>
* Hofmeister F. (1888) ''Arch. Exptl. Pathol. Pharmakol.'', '''24''', 247.
* Zhang Y and Cremer PS. (2006) ''Curr. Opin, Chem. Biol.'', '''10''' (6), 658-63. PMID 17035073
* Zhou HX. (2005) ''Proteins'', '''61''' (1), 69-78. PMID 16044460
* Tanford C and Reynolds J. (2001) ''Nature's robots: a history of proteins'', Oxford University Press. ISBN 0-19-850466-7
* Creighton TE. (1993) ''Proteins'', 2nd ed., W. H. Freeman. ISBN 0-7167-2317-4
* Jencks WP. (1969) ''Catalysis in Chemistry and Enzymology'', Dover republication (1987). ISBN 0-486-65460-5
* Collins KD.; Washabaugh MW. (1985) The Hofmeister effect and the behaviour of water at interfaces ''Q Rev Biophys'' '''18''' (4) PMID 3916340
[[Category:Biochemists|Hofmeister, Franz]]
[[Category:German chemists|Hofmeister, Franz]]
[[Category:1850 births|Hofmeister, Franz]]
[[Category:1922 deaths|Hofmeister, Franz]]
[[de:Franz Hofmeister]]