AMINO ACID STEREO CONFIGURATION

                                                Copyright: J. E. Wampler, 1996

Topics Covered:

Notation and Assignment
Amino Acid Configuration at the Alpha Carbon
Second Optical Center in Threonine and Isoleucine

Optical activity (quantified by the rotation of the plane of polarized light as it passes through a substance) was measured long before the three dimensional structure of molecules could be determined by methods such as X-ray Crystallography. The experimental assignment of optical activity was then symbolized with the letter "d" or the "+" sign (for dextrotatory, right handed or clockwise rotation of the plane of polarized light when viewed toward the light source) and "l" or "-" (for levorotatory, left hand or counterclockwise rotation).

Later the "D" and "L" symbols were associated with absolute configuration based on the arbitrary, but as it turned out, correct assignment of the absolute configuration of the dextrotatory and levorotatory forms of glyceraldehyde. In this symbolism, absolute configuration is based on chemical synthesis starting with glyceraldehyde (Fischer and Rosanoff) and optical activity is specified using the "+" and "-" notation.

A second absolute configuration notation using the symbols R (from rectus, latin for right) and S (from sinister, latin for left) was developed by Cahn, Ingold & Prelog. In this approach, the substituents on an assymetric carbon (eg. a tetrahedral carbon with four different substituents) are prioritized by decreasing atomic number. Configuration is assigned by "looking" down the bond to the lowest priority substituent and assigning R to the configuration where the remaining subtituents are arranged clockwise in decreasing priority. S is then assigned to the molecular form where the substituents are arranged counterclockwise.

Some other rules for assigning R/S configuration:

Group Priorities: SH > OH > NH2 > COOH > CHO > CH2OH > C6 H5 > CH3 > H

Larger groups are ranked at their points of divergence, i.e. a CH2CH2SH is greater than a CH2CH2OH

The absolute stereo configuration of the amino acids at the alpha carbon is typically referred to using the D/L notation with reference to the absolute configuration of Glyceraldehyde rather than the more modern R/S designation. In R/S notation change of a single substituent can change assignment. However, all of the amino acids used in proteins (except for glycine which is not optically active) are of L configuration. However, in R/S notation cysteine is 2R, whereas the others are 2S.

Both threonine and isoleucine have a second assymetric carbon center at carbon position 3 along their chains. The absolute configuration of the normal protein component, L-threonine, is 2S,3R. The mirror image compound (the enantiomer) is D-threonine (2R,3S). The diastereomer with 2S, 3S configuration is called L-allo-threonine (D-allo-threonine is then 2R, 3R). For isoleucine, the configuration of normal L-isoleucine is 2S, 3S.

NOTE: While L-threonine and L-isoleucine have different R/S configurations, the two molecules can be superimposed, i. e. the arrangement of the methyl group, the hydrogen atom and the backbone atoms are the same.

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