Polypeptide esters

There are a number of useful synthetic applications of these reactions of chelated amino acid esters (Fig. 3-12). For example, if the attacking nucleophile is not a simple amine, but is another amino acid ester or an O-protected amino acid, then peptide or polypeptide esters are formed in excellent yields. This may be developed into a general methodology for the metal-directed assembly (and, in the reverse reaction, the hydrolysis) of polypeptides. 

Hydrolysis of polypeptide esters. Bu NOH is useful for hydrolysis with minimum... 

Abdel-Magid,A. F. Cohen,J. H. MaryanofF, C. A. Shah, R. D. Villani, F. J. Zhang, F., Hydrolysis of Polypeptide Esters with Tetrabutylammonium Hydroxide. Tetrahedron Lett. 1998, 39, 3391. 

It was observed by Curtius and Gumlich that the biuret base when heated in vaaio to 100° C. lost alcohol, and that it was converted into an anhydride, most probably octoglycine anhydride, so that from glycine ester quite complex substances can be obtained. Such substances have also been obtained by Emil Fischer and his pupils by the condensation of amino acid and polypeptide esters (see below). 

These compounds already exhibit the extraordinary possibilities of synthesis by this method. By continuing the process of preparing the acid chloride of a new polypeptide and again combining it with a polypeptide ester, the synthesis of the complex octadecapeptide, composed of fifteen glycine residues and three leucine residues, was effected in 1907. Its preparation is the best illustration of how this method lends itself to the synthesis of the polypeptides. 

Our continued search for better alternatives to traditional saponification procedures led to the use of tetraalkylammonium hydroxides. Tetraalkylammonium hydroxides are very strong bases and have the advantage of being soluble in water and in many organic solvents. However, these bases, except for some scattered reports, were not fully utilized in carboxylic ester hydrolysis, particularly for polypeptide esters. The use of tetraalkylammonixim hydroxides in hydrolysis of small easily soluble polypeptide esters does not show much of an advantage over the traditional conditions such as NaOH in aqueous acetone. However, fully-protected larger polypeptide chains, which show... 

We applied this hydrolysis procedure to many polypeptide esters, and for large-scale production of several polypeptide acids.[7] An exanq>le that shows the advantage of this procedure over o er procediures is the hydrolysis of the sinq>le noiq>olar polypeptide ester Boc-LLLLLL-OMe. Using 40% aqueous ( -Bu)4NOH (2 equiv.) in DMF at 0 °C, the reaction is conq)lete in 2h giving an isolated yield of 85% and diastereomer ratio of 99.4 0.6. Conq>are to the reaction with aqueous NaOH (2 equiv.) in DMF at 25 °C only 50% conq>lete after 3 days with diastereomer ratio of 98.8 1.2. This and other exanq>les (7) show clearly that diis is a superior procedure. 

The solution phase synthesis of the pulmonary surfactant 21-amino acid polypeptide, KL4 was achieved in two different synthesis approaches. The first approach was a linear fragment synthesis that suffered from the low solubility of the larger fragments latter in the synthesis. A convergent approach was developed to minimize these effects and inqirove both yield and purity of the final product. An efficient procedure for the hydrolysis of large polypeptide esters with tetraalkylammonium hydroxides was developed and applied successfully to the synthesis of the key 8-amino acid polypeptide intennediate 25. 

One widely used method of formation of protected compounds involves polymer-supported reagents, with the advantage of simple workup by filtration and automated syntheses, especially of polypeptides. Polymer-supported reagents are used to protect a terminal — COOH group as a polymer-bound ester (RCOOR —( ) during peptide syntheses, to protect primary alcohols as... 

A variety of cellular and viral proteins contain fatty acids covalently bound via ester linkages to the side chains of cysteine and sometimes to serine or threonine residues within a polypeptide chain (Figure 9.18). This type of fatty acyl chain linkage has a broader fatty acid specificity than A myristoylation. Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the Cjg and Cjg chain lengths being most commonly found. Proteins anchored to membranes via fatty acyl thioesters include G-protein-coupled receptors, the surface glycoproteins of several viruses, and the transferrin receptor protein. 

Transfer RNA (tRNA) serves as a carrier of amino acid residues for protein synthesis. Transfer RNA molecules also fold into a characteristic secondary structure (marginal figure). The amino acid is attached as an aminoacyl ester to the 3 -terminus of the tRNA. Aminoacyl-tRNAs are the substrates for protein biosynthesis. The tRNAs are the smallest RNAs (size range—23 to 30 kD) and contain 73 to 94 residues, a substantial number of which are methylated or otherwise unusually modified. Transfer RNA derives its name from its role as the carrier of amino acids during the process of protein synthesis (see Chapters 32 and 33). Each of the 20 amino acids of proteins has at least one unique tRNA species dedicated to chauffeuring its delivery to ribosomes for insertion into growing polypeptide chains, and some amino acids are served by several tRNAs. For example, five different tRNAs act in the transfer of leucine into... 

The reaction product with monoethanolamine acts as a thickening agent [41,101] and with alcohols as an emollient [40]. Also reaction products with amino acids and oligo- or polypeptides for use in cosmetic formulations are known [43]. Sorbitan esters from ether carboxylates are described as emulsifiers or mild surfactants in cosmetic formulations [39] and alkyl ether carboxylic acid taurides as nonirritant anionic surfactants for cosmetic cleaners in particular [44]. Using unsaturated ether carboxylates it is possible to make viscous formulations based on combinations of unsaturated and saturated ether carboxylates [111]. Highly purified alkyl ether carboxylates based on alcohol ethoxylates with low free alcohol content have also been described [112]. 

Finally, a new water-soluble polyphosphazene was recently synthesized that has the structure shown in 36 (46). This polymer has two attributes as a biomedical macromolecule. First, the pendent carboxylic acid groups are potential sites for condensation reactions with amines, alcohols, phenols, or other carboxylic acid units to generate amide, ester, or anhydride links to polypeptides or bioactive small molecules. Second, polymer forms ionic crosslinks when brought into contact with di- or trivalent cations such as Ca or Ai3+. The crosslinking process converts the water-soluble polymer to a hydrogel, a process that can be reversed when the system... 

CpCpApCpCpA and this hexanucleotide has been prepared from appropriately protected trinucleotides using a sulphonyl chloride as condensing agent.2 (3 )-0-Glycyl esters of Cpl and dCpA have been prepared as potential substrates of ribosomal peptidyl transferase. While the glycyl ester of Cpl released the polypeptide chain from polylysyl-tRNA in a ribosomal system from E. coli, the dCpA derivative showed little activity. 

The free amino group of the amino ester may then react analogously with another molecule of the monomer, etc. The kinetics of the polymerization are in harmony with a mechanism of this sort. The final polypeptide may contain up to 300 or more structural units. While the polymerization of N-carboxyanhydrides is closely analogous to the addition polymerizations of ethylene oxide and of other cyclic substances, definition unfortunately classifies it as a condensation polymerization inasmuch as carbon dioxide is eliminated in the process. 

Many enzymes have absolute specificity for a substrate and will not attack the molecules with common structural features. The enzyme aspartase, found in many plants and bacteria, is such an enzyme [57], It catalyzes the formation of L-aspartate by reversible addition of ammonia to the double bond of fumaric acid. Aspartase, however, does not take part in the addition of ammonia to any other unsaturated acid requiring specific optical and geometrical characteristics. At the other end of the spectrum are enzymes which do not have specificity for a given substrate and act on many molecules with similar structural characteristics. A good example is the enzyme chymotrypsin, which catalyzes hydrolysis of many different peptides or polypeptides as well as amides and esters. 

As early as five years after the Miller-Urey experiments, Schramm and Wissmann from the Max Planck Institute for Virus Research in Tubingen reported a successful synthesis of polypeptides using polyphosphate esters. Thus, they were able to... 

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