Aromatic short-chain peptides

While cyclic peptides have proven to be problematic, we beheve that amino acids are ideal candidates for derivatization of our macrocyclic scaffolds. Mary natural and unnatural amino acids with appropriately protected side chains are commercially available or can be readily prepared providing facile access.22 The a-amino- and a-carboxy- groups common to all of these will provide constant sites for attachment to a macrocyclic scaffold core. Side chains varying in aromatic, aliphatic, polar and ionic characters should provide sufficient chemical diversity. Finally, amino acids may be combined in many ways to form short acyclic peptides, allowing access to more diverse chemical properties not found in individual amino acids. 

The plot of In fcgt vs. the number, n, of Pro residues (Figure 1) demonstrates that for longer hnear peptides (n = 3-5), the rate of electron transfer decreases exponentially with growing n. However, the k t data for shorter (n = 0-2) hnear peptides fall off considerably from the plot extrapolated to lower n values. This indicates that the rate of LRET in short-bridged peptides is faster than would be expected on the assumption of a common mechanism of electron transfer in the whole group of peptides. In order to rationahze these findings in terms of the theory of the distance dependence of LRET kinetics (33, 34), the separation distances and spatial disposition of the aromatic side chains in the hnear peptides studied had to be evaluated from their conformational preferences and conformational dynamics. 

It is seen that there is a preponderance of aliphatic chains present long chains contributed by the two leucine fragments, short chains contributed by alanine fragments. The only polar groups are the peptide bonds themselves and the two aromatic rings from the phenylalanine fragments that could produce induced dipoles. It follows that the overall character of the hexapeptide is likely to be dispersive and thus, the peptide would probably be defined as hydrophobic or lyophobic in nature. 

Many proteins contain hundreds of amino acids. To determine their sequences other reactions are required to provide sequences short enough to be determined by Edman degradation. Enzymatic cleavage by two enzymes, trypsin and chymotrypsin, is used to produce smaller peptides. Trypsin cleaves polypeptide chains on the C-terminal side of basic residues such as arginine and lysine. Chymotrypsin cleaves the polypeptide on the C-terminal side of aromatic residues. 

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