Stereochemistry of Polypeptides

Proteins contain 20 different R groups actually there are 19 different amino acid side chains or R groups and the 20th, which is proline, is a ring 

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Ramachandran GN, Ramakrishnan C, Sasiekharan V. Stereochemistry of polypeptide chain configurations. J Mol Biol 1963 7 95-99. 

Ramachadran G N, C Ramakrishnan and V Sasiekhaian 1963. Stereochemistry of Polypeptide Chain Configurations Journal of Molecular Biology 7 95-99... 

Ramachandran, G. N., Ramakrishnan, C., 8c Sasisekharan, V. (1963). Stereochemistry of polypeptide chain configurations. Journal of Molecular Biology, 7, 95. 

Considerable understanding of the stereochemistry of polypeptide chains was gained from theoretical and experimental studies... 

The stereochemistry of step polymerization is considered now. Bond formation during step polymerization almost never results in the formation of a stereocenter. For example, neither the ester nor the amide groups in polyesters and polyamides, respectively, possess stereocenters. Stereoregular polymers are possible when there is a chiral stereocenter in the monomer(s) [Oishi and Kawakami, 2000 Orgueira and Varela, 2001 Vanhaecht et al., 2001], An example would be the polymerization of (R) or (S)-H2NCHRCOOH. Naturally occurring polypeptides are stereoregular polymers formed from optically active a-amino acids. 

Banerjee A, Balaram P. Stereochemistry of peptides and polypeptides containing oo-amino acids. Curr. Sci. 1997 73 1067-1077. 

The potential application of the Ugi four-component reaction for amino acid and polypeptide natural product synthesis was recognized and utilized early on by M.M. Joullie." " A representative example is the total synthesis of (+)-furanomycin, a naturally occurring antibiotic. As the exact stereochemistry of the compound was not confirmed, total synthesis of the natural product and its stereoisomers was used to elucidate the stereochemistry. 

There is also a crucial problem of stereochemistry in the synthesis of polypeptides. Natural proteins consist of L-amino acids, and any racemization at the chiral centers has a profound effect on the structure and biological activity. Altered stereochemistry drastically changes the three-dimensional shape of a polypeptide chain, and this three-dimensional structure is normally essential for the biological function of the polypeptide. 

The second very important conclusion is related to the nature of the covalent bond between the nitrogen and the carbon atom. This bond has a single bond character in one of the resonance structures and a double bond character in the other. Hence, the amide bond has a bond order of 1.5, i.e. it has an intermediate character between a double and a single bond. In the chapter on alkanes we have mentioned that while the rotation around a single bond is free, the rotation around a double bond is forbidden. Because the amides bond has a partial double bond character the rotation around it is hindered. This evidence is important in the study of the stereochemistry of complex molecules with amide groups, such as polyamides and polypeptides. 

By knowing the active intermediates in these polymerizations, Cheng and Deming were also able to use chiral donor ligands to prepare optically active nickel initiators for the enan-tioasymmetric polymerization of NCAs. Since polypeptides are chiral polymers, the ability to control stereochemistry during polymerization is a feature worth pursuing. This is especially true since the self-assembly and properties of polypeptides are critically dependent on the stereochemistry of the amino acid components. Due to constraints imposed by the initial... 

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