Franz Hofmeister (30 August 1850, in

Prague Prague ( ; ) is the capital and List of cities and towns in the Czech Republic, largest city of the Czech Republic and the historical capital of Bohemia. Prague, located on the Vltava River, has a population of about 1.4 million, while its P ...

– 26 July 1922, in

Würzburg Würzburg (; Main-Franconian: ) is, after Nuremberg and Fürth, the Franconia#Towns and cities, third-largest city in Franconia located in the north of Bavaria. Würzburg is the administrative seat of the Regierungsbezirk Lower Franconia. It sp ...

) 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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s linked by

peptide bond In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...

s, although this model of protein

primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

was independently and simultaneously conceived by

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

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 and the ...

. 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 chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thus, ...

. 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 to be excluded by water. The word hydrophobic literally means "water-fearing", and it describes the segregation of water and nonpola ...

. 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'', ''Cerati ...

). Ions that have a strong '' salting in'' 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 compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

. 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 long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the dig ...

. 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 anion, an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,... ...

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 Biuret ( ) is a chemical compound with the chemical formula . It is a white solid that is soluble in hot water. A variety of organic derivatives are known. The term "biuret" also describes a family of organic compounds with the chemical formula , ...

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 Chemists from Austria-Hungary Emigrants from Austria-Hungary to Germany 20th-century German chemists 19th-century German chemists German biochemists German Bohemian people Scientists from Prague Academic staff of Charles University