Peptide stereochemistry

Miao, V., Coeffet-Le Gal M.-F. et al. (2005) Daptomycin biosynthesis in Streptomyces roseosporus cloning and analysis of the gene cluster and revision of peptide stereochemistry. Microbiology (Reading, England), 151,1507. 

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.]...

Proteins are large biomolecules made up of a-amino acid residues linked together by amide, or peptide, bonds. Chains with fewer than 50 amino acids are often called peptides, while the term protein is reserved for larger chains. Twenty amino acids are commonly found in proteins all are a-amino acids, and all except glycine have stereochemistry similar to that of l sugars. In neutral solution, amino acids exist as dipolar zwitterions. 

As a result of their capacity to tolerate very different kinds of y9-peptidic turns (120 versus 122) and different stereochemistries in the turn segment (compare S/ R and R/S nipecotic acid dipeptide sequences), hairpin stmctures formed by fS-peptides reveal unusually high plasticity compared to a-peptide y9-hairpins. 

Adamantane can be used to construct peptidic scaffolding and synthesis of artificial proteins. It has been introduced into different types of synthetic peptidic macrocycles, which are useful tools in peptide chemistry and stereochemistry studies and have many other applications as well. Introduction of amino acid-functionalized adamantane to the DNA nanostmctures might lead to construction of DNA-adamantane-amino acid nanostmctures with desirable stiffness and integrity. Diamondoids can be employed to constmct molecular rods, cages, and containers and also for utilization in different methods of self-assembly. In fact, through the development of self-assembly approaches and utilization of diamondoids in these processes, it would be possible to design and constmct novel nanostmctures for effective and specific carriers for each dmg. 

Racemisation is a chemical reaction, and its rate is different for each type of amino acid. An important fact is that this process is affected by many factors that influence the rate of change of the amino acids stereochemistry [106]. The main parameters affecting the racemisation process include the amino acid structure, the sequence of amino acids in peptides, the bound state versus the free state of the amino acids, the pH in the environment, the concentration of buffer compounds, the contact of the sample with clay surfaces... 

Recent studies by Grubbs on the effect of stereochemistry on synthesis of macrocyclic peptides (disubstituted alkenes) by ring closing metathesis were not disclosed at the time of our planning. See (a) Ref. 6a. (b) Miller SJ, Blackwell H, Grubbs RH (1996) J Am Chem Soc 118 9606... 

The relevant AGB values, calculated by using Te = 970 are listed in Table 8. According to the reported values, the heterochiral Trp/Pro and Phe/Ala complexes are more stable than the homochiral ones. The reverse is true for the Phe/ Pro and PheA al complexes. By the same token, the chiral discrimination factor, AR measured by ESl-MS for 19 amino acids was found to vary between 0.3 and 3. ° The stereochemistry associated to the CID of diastereomeric peptides has been investigated using a similar approach. The results suggest that the secondary structure of protonated peptides may play an important role in their gas-phase behavior. ... 

Annis, D. A. Helluin, 0. Jacobsen, E. N. (1998) Stereochemistry as a diversity element solid-phase synthesis of cyclic RGD peptide derivatives via asymmetric Catalysis., Chem., Int. Ed. Engl, 37, 1907-1909. 

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