Polypeptides stereochemistry

Polypeptide Stereochemistry (Goodman, Verdini, Choi and Masudo). 5 69... 

Goodman, M., Concepts of Polymer Stereochemistry, 2, 73 Polypeptide Stereochemistry, 5, 69. 

Figure 18.12 The electron-density map is interpreted by fitting into it pieces of a polypeptide chain with known stereochemistry such as peptide groups and phenyl rings. The electron density (blue) is displayed on a graphics screen in combination with a part of the polypeptide chain (red) in an arbitrary orientation (a). The units of the polypeptide chain can then be rotated and translated relative to the electron density until a good fit is obtained (b). Notice that individual atoms are not resolved in such electron densities, there are instead lumps of density corresponding to groups of atoms. [Adapted from A. Jones Methods Enzym. (eds. H.W. Wyckoff, C.H. Hirs, and S.N. Timasheff) 115B 162, New York Academic Press, 1985.]...

Protein polymers based on Lys-25 were prepared by recombinant DNA (rDNA) technology and bacterial protein expression. The main advantage of this approach is the ability to directly produce high molecular weight polypeptides of exact amino acid sequence with high fidelity as required for this investigation. In contrast to conventional polymer synthesis, protein biosynthesis proceeds with near-absolute control of macromolecular architecture, i.e., size, composition, sequence, topology, and stereochemistry. Biosynthetic polyfa-amino acids) can be considered as model uniform polymers and may possess unique structures and, hence, materials properties, as a consequence of their sequence specificity [11]. Protein biosynthesis affords an opportunity to completely specify the primary structure of the polypeptide repeat and analyze the effect of sequence and structural uniformity on the properties of the protein network. 

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. 

One of the aspects of structural complexity in biomolecules is that of stereochemistry. To the increase in stereochemical complexity when going to larger biomolecules correspond new stereochemical features and properties. Thus, the concepts of cycloenantiomerism, cyclodiastereoisomerism and cyclostereoisomerism have been introduced by Prelog and collaborators [118-120] to describe stereochemical features of cyclic molecules displaying 2n centers of chirality, e.g., cyclic polypeptides. 

Computations on simple systems and comparison of the results with experiment have provided confidence in the validity and applicability of the foregoing approach. Considering the fundamental structures adopted by polypeptide chains, the a helix and the (3 sheet, their stereochemistry has been elucidated by such calculations. 

To date, the most extensively studied natural ionophore is gramicidin,10 a polypeptide antibiotic isolated from the bacterium Bacillus brevis. Indeed, the idea of a channel-like structure for ion transport was inferred from its study. However, unlike channel proteins, which are exclusively composed of L-amino acids, each alternate amino acid in gramicidin has D-stereochemistry. It is composed of 16 residues, 15 of which are amino acids. The structure is summarized below, in which Xxx has the following identities gramicidin A (gA), Trp gB, Phe gC, Tyr gD, a mixture of gA, gB, gC, -80 5 15. 

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

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