Peptides interesting examples

Other interesting examples of proteases that exhibit promiscuous behavior are proline dipeptidase from Alteromonas sp. JD6.5, whose original activity is to cleave a dipeptide bond with a prolyl residue at the carboxy terminus [121, 122] and aminopeptidase P (AMPP) from E. coli, which is a prohne-specific peptidase that catalyzes the hydrolysis of N-terminal peptide bonds containing a proline residue [123, 124]. Both enzymes exhibit phosphotriesterase activity. This means that they are capable of catalyzing the reaction that does not exist in nature. It is of particular importance, since they can hydrolyze unnatural substrates - triesters of phosphoric acid and diesters of phosphonic acids - such as organophosphorus pesticides or organophosphoms warfare agents (Scheme 5.25) [125]. 

Overall, these chitinase inhibitors provide an interesting example of peptide-carbohydrate mimicry. As described above for several other systems, mimicry consists of a mixture of structurally mimetic interactions and other favorable interactions with the receptor. Of the structurally mimetic interactions, the mimicry by argifin of the N-acetyl group, and part of the pyranosyl... 

An interesting example of scale-up of peptide synthesis in such low-melting point mixtures derived from eutectic melts has been described [70]. Neat combination of the pure substrates in the complete absence of water/solvent (adjuvant) provided simple heterogeneous systems consisting of the eutectic melts plus an excess of solid substrate (Figure 12.5). 

Another interesting example reported recently is the peptide mimetic 1 (Figure 8), which is a small molecule inhibitor of the IL-2-IL-2Ra receptor interaction.47... 

The Wolff rearrangement and the Arndt-Eistert homologation sequence are very useful in organic synthesis. One of the most popular applications involves amino acids. An interesting example has been described as a key reaction in the synthesis of a 14C-labeled amino acid used for deciphering the biosynthesis of penicillin N from glutamic acid (Scheme 3.2).9 This rearrangement proceeds without racemization and can thus be applied in peptide synthesis. 

Another interesting example of the application of clusters to a problem in a different area of chemistry is the use of the Mo2 + unit to complex peptides in such a way that they retain their natural conformations, which can then easily be studied by X-ray crystallography (53). 

The application of the non-urethane PhAc blocking group results in ca. 6% racemization during the construction of the phenylacetamido-protected dipeptides by chemical activation of the phenylacetamido amino acids. This disadvantage can be overcome by forming the peptide bonds enzymatically, e.g. with trypsin [26,27], chymotrypsin [26,28], or carboxypeptidase Y [26,29]. An interesting example is the biocatalyzed synthesis of leucine-enkephalin tert-butyl ester [25e], in which phenylacetamides are introduced and cleaved by means of penicillin G acylase, and the elongation of the peptide chain is carried out with papain or a-chymotrypsin. 

An interesting example of a branched trimer containing (1 6)- and /3(1 2)-amide-linked sugars was supplied by Sicherl and Wittmann who devised mimetics of amino glycosides [37]. Pioneered by the group of Kessler [38] pyranoid sugar amino acid templates were described to represent turn mimetics and model peptides [39,40] including cyclic peptides [41,42]. As... 

Many protein-ligand complexes are characterized by the presence of both polar and lipophilic interactions. The bound conformation of the ligand is determined by the relative importance of these contributions. An interesting example highlighting several important aspects was recenfly described by Lange and co-workers using the binding of non-peptidic inhibitors to the SH2 domain of src kinase [28]. The inhibitors are essentially tetrapeptide mimetics with tyrosine-phosphate or a... 

An interesting example taking the opposite approach was presented by Wieczorek et al. [24]. To separate a mixture of dipeptide diastereoisomers and their phosphonic analogues, achiral crown ethers were used as transport enhancers. In this case, the diastereomeric complex is formed between the chiral transported molecule and not the optically active carrier. The observed stereoselectivity depends on the peptide structure and was independent of the presence of carrier, but the application of carrier increased the transport rate of both diastereoisomers. 

Schlunnegger et al. [214a] cited an interesting example corresponding to the second case. The B/ linked scan spectrum of the m/z 227 fragment ion, produced by the decomposition of AcN-Leu-Ala-Leu-OCHj, is characterized by a very intense peak at ra/z 188 (base peak), corresponding to the elimination of a 39 u fragment, which is impossible when the structure of this peptide is considered. 

Although their structures are less complex than the larger protein molecules, peptides have significant biological activities. The structure and function of several interesting examples, presented in Table 5.3, are now discussed. 

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