Amino Acids

The Subunits of Proteins

Introduction
Amino acids represent a class of molecules defined by one property: all amino acids (found in proteins) possess a carboxylic acid group and an amino group; both linked to a single carbon atom, called the alpha-carbon, hence the name alpha-amino acid. With the exception of glycine, all alpha-carbons are asymmetric resulting in optical active isomers. As in sugars, these are called the D- and L-isomers. Up to date only L-isomers have been found in all known mammalian and plant cells. However, D-isomers exist in cell membranes of some bacteria and invertebrates. In proteins and peptides, the carboxylic group of one amino acid is linked to the alpha-amino group of the neighboring amino acid; this covalent bond is called peptide bond, building long chains. Chemically peptide bonding is a condensation reaction between two amino acids with the loss of one molecule of water and called an amide bond. Depending on the physical features of the amino acid building blocks, the protein chain folds into a unique and biochemically specific three-dimensional structure. In the cell, protein synthesis follows a highly conserved mechanism, determined by the genetic code, a three-nucleotide sequence of DNA or RNA, respectively. Each codon stands for one amino acid, so the protein sequence is an accurate translation of the DNA (mRNA) sequence [1, 2].

Some examples for amino acids and peptides:

D-Alanine        L-Alanine
D-Alanine                  L-Alanine


TRH-Peptide
TRH Peptide

Properties of Amino Acids

Amino acids are crystalline substances with high melting points (above 200 °C). At physiological pH, both carboxylic and amino groups are ionized. Their chemical diversity comes from the side chain attached to the alpha-carbon and they are grouped according to whether their chain is acidic or basic or uncharged polar or non-polar.

Amino acid1-letter symbol3-letter symbolSide chain
Aspartic acid Asp D negative
Glutamic acid Glu E negative
Arginine Arg R negative
Lysine Lys K positive
Histidine His H positive
Asparagine Asn N uncharged polar
Glutamine Glu Q uncharged polar
Serine Ser S uncharged polar 
Threonine Thr T uncharged polar 
Tyrosine Tyr Y uncharged polar
Alanine Ala A non-polar
Glycine Gly G non-polar
Valine Val V non-polar
Leucine Leu L non-polar
Isoleucine Ile I non-polar
Proline Pro P non-polar
Phenylalanine Phe F non-polar
Methionine Met M non-polar
Tryptophan Trp W non-polar
Cycteine Cys C non-polar

 

Besides isolation of amino acids from natural materials, biotechnical synthesis either in microorganisms and /or enzymatically is the best way to get optical pure isomers at large scales. Usually chemical synthesis results in optical inactive racemates (1:1 ratio of D and L), which are hard to separate [1, 2].

Natural and Non-Natural Amino Acids

More than 78 different amino acids have been found in meteorites. Nature as we know has selected twenty amino acids, nine of them are essential, meaning not synthesized in the organism and have to be obtained by food intake. Only these twenty are called natural amino acids, all other amino acids even with the slightest modification are non-natural amino acids. The reason why evolution settled on this particular set of amino acids is a mystery. The selection seems to be random.
However, despite or rather because of this fact, artificial amino acids became a point of interest for biochemists. By creating de novo proteins in vitro, scientists seek help to answer the basic questions of protein folding and specificity. It is possible to incorporate a comparably large number of artificial amino acids into either natural or non-natural proteins. Substitution of methionine by selenomethionine has improved resolution for x-ray diffraction analysis for direct structure determination of proteins [3,4]. Peptides made from novel amino acids are less prone to recycling in the organism than their natural counterparts and make useful drugs [5]. Engineered proteins and enzymes from novel amino acids find their application as industrial catalysts. De Novo enzymes can develop an increase in stability and activity at non-physiological conditions and possibly lose their rigid substrate selectivity.
The design of artificial amino acids raises the question of new genetic coding schemes and engineered bacteria with a 21 amino acid genetic code have been reported [6].

Homoserine
ß-Homoserine

Allylglycine
Allylglycine

Amino Acids as Chiral helpers

Proteins or enzymes can be very helpful to catalyze all kinds of difficult chemical reactions but are usually hard to handle and/ or are very expensive. However, single amino acids are less expensive and more durable. They proved to be helpful in directing asymmetric reactions towards high enantioselectivity. Modified proline called RAMP and SAMP are used for enantioselective alkylation of ketones [7].

RAMP
RAMP


L-proline catalyzed Mannich-type reaction leads to a variety of further amino acids with excellent enantioselectivities and opens new avenues to chemical synthesis [8].

Assymetric-Mannich-reactions
Asymmetric Mannich reactions

Direct asymmetric aldol reactions catalyzed by amino acids and small peptides yield up to 99% enantiomeric excess in the aldol products. The fact that small peptides turned out such powerful chiral helpers suggests that ancient amino acid oligomers might be the link to the homochirality of sugars [9].

Assymetric-Aldol-Reactions
Asymmetric aldol reactions

Amino Acid Derivatives

Amino acid structures are found in many commonly used substances i.e. aspartame (sweetener) and monosodium glutamate (flavor enhancer). Drugs like 5-hydroxy tryptophane and L-DOPA allow neurological problems like depression and Parkinson disease, respectively, to be treated.

L-Glutamic-acid
L-Glutamic acid monosodium salt

Aspartame
Aspartame



Selection of Biosynth's Products
Cat.No - Product Name
A-4650 - L-Albizziine
A-0200 - 2-Acetamidoacrylic acid
A-6060 - 2-Aminoisobutyric acid ethyl ester hydrochloride
D-1080 - DL-2,4-Diaminobutyric acid dihydrochloride
D-3800 - 3,5-Diiodo-L-tyrosine dihydrate
L-9000 - D-Lysine monohydrochloride
P-7200 - D-Proline

Literature
[1] Molecular Biology of the Cell, Fourth Edition, Garland Science, 2002.
[2] Römpp Lexikon Biotechnologie, 9. Auflage, Thieme Verlag, 1992.
[3] D.B. Corrie, G.N. Cohen, Biochim. Biophys. Acta, 26, 1957, 252.
[4] W.A. Hendrickson et al, EMBO J, 9, 1990, 1665.
[5] C. Merryman, R. Green, Chemistry and Biology, Vol.11, 2004. 575.
[6] R.R. Mehl et al, J. Am. Chem. Soc., 2003. 125.
[7] Römpp Lexikon Chemie, 10. Auflage, Thieme Verlag
[8] A. Cordova et al, J. Am. Chem. Soc., 2002. 124.
[9] A. Cordova et al, Chemistry, 2006, Jul 5, 12 (20)

Biosynth Web Shop

Wide variety. Swiss quality.

Browse our full catalog, as well as items available for online purchase:

Products


footerBackground