Franz Hofmeister (30 August 1850, in

Prague Prague ( ; cs, Praha ; german: Prag, ; la, Praga) is the capital and List of cities in the Czech Republic, largest city in the Czech Republic, and the historical capital of Bohemia. On the Vltava river, Prague is home to about 1.3 milli ...

– 26 July 1922, in

Würzburg Würzburg (; Main-Franconian: ) is a city in the region of Franconia in the north of the German state of Bavaria. Würzburg is the administrative seat of the ''Regierungsbezirk'' Lower Franconia. It spans the banks of the Main River. Würzburg ...

) was an early protein scientist, and is famous for his studies of salts that influence the solubility and conformational stability of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s. In 1902, Hofmeister became the first to propose that polypeptides were

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

s linked by peptide bonds, although this model of protein primary structure was independently and simultaneously conceived by

Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fischer projection, a symbolic way of draw ...

Early life

Hofmeister's father was a doctor in Prague, where Hofmeister first began his studies, under the physiologist Karl Hugo Huppert, himself a student of Carl Lehmann. Hofmeister's ''Habilitationsschrift'' in 1879 concerned the peptic products of digestion. Hofmeister became a Professor of Pharmacology at the First Faculty of Medicine, Charles University in Prague in 1885, then eventually moved to Strasbourg in 1896.

The 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 and

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may i ...

. Anions appear to have a larger effect than cations, and are usually ordered :

\mathrm

(This is a partial listing; many more salts have been studied.) The order of cations is usually given as :

\mathrm

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 In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

. 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 The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in an aqueous solution and exclude water molecules. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpolar ...

. 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 Pancreatic ribonuclease family (, ''RNase'', ''RNase I'', ''RNase A'', ''pancreatic RNase'', ''ribonuclease I'', ''endoribonuclease I'', ''ribonucleic phosphatase'', ''alkaline ribonuclease'', ''ribonuclease'', ''gene S glycoproteins'', ''Ceratit ...

). Ions that have a strong ''

salting in Salting in refers to the effect where increasing the ionic strength of a solution increases the solubility of a solute, such as a protein. This effect tends to be observed at lower ionic strengths. Protein solubility is a complex function of p ...

'' effect such as I⁻ and SCN⁻ 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. Moreover, they may have direct interactions with some standard hydrophobic molecules, e.g.,

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...

. A quantum chemical investigation suggests an electrostatic origin of the Hofmeister series, which appears to quantify this qualitative series (at least for anions).

Protein purification

The importance of the Hofmeister series to early protein work should not 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 favourite 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 Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting these long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the d ...

. R=C-N-C=R bonds could be eliminated because it would imply a much larger number of

carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...

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.

References

External links

* {{DEFAULTSORT:Hofmeister, Franz 1850 births 1922 deaths 20th-century German chemists 19th-century German chemists German biochemists German Bohemian people Scientists from Prague Charles University faculty