Carboxyl group, carboxylate peptides

The pentaaminecobalt(III) complex has been prepared from amino acids to protect the carboxyl group during peptide synthesis [(H20)Co(NH3)5(C104)3, 70 , H2O,... 

Developed as a carboxyl protective group for peptide synthesis because of its stability to hydrogenolysis and acidic conditions, the acetol (hydroxy acetone) ester is prepared by DCC coupling (68-92% yield) of the acid with acetol. It is cleaved with TBAF in THF. ... 

FIGURE 3.20 Protection of carboxyl groups by esterification of V-protected amino acids (A) by reaction of the anion with an alkyl halide or haloalkyl resin (R = resin) in dimethylformamide51 and (B) by tertiary amine-catalyzed reaction of a symmetrical anhydride with hydroxymethylphenyl-resin (R = resin).53 The intermediate is probably that depicted in Figure 3.19. Reaction (A) is applicable also to the carboxyl groups of peptides. 

F Weygand, A Prox, W Konig. Racemization of the penultimate amino acid with a terminal carboxyl group in peptide synthesis. Chem Ber 99, 1446, 1966. 

Usually, linkers are bifunctional molecules one functionality is for connection to the solid support, and the other is a selective cleavable functional group. Because peptide synthesis was more or less the only application for solid-phase chemistry in its early days, most of the linkers were developed to supply amines or carboxylic acids after cleavage. 

By convention, the left-hand amino acid in this sequence is the one with a free amino group, the A-terminus, and the right-hand amino acid has the free carboxyl, the C-terminus. Thus, Ser-Phe-Ala is different from Ala-Phe-Ser, and represents a quite different molecule. Sometimes, the termini identities are emphasized by showing H- and -OH H- represents the amino group and -OH the carboxyl group. Some peptides are cyclic, and this convention can have no significance, so arrows are incorporated into the sequence to indicate peptide bonds in the direction CO— NH. As sequences become longer, one-letter abbreviations for amino... 

Proteins bind Ca "" via oxygen ligands, particularly carboxylate groups and carbonyl groups of peptide bonds. This also applies to the structure illustrated here, in which a Ca "" ion is coordinated by the oxygen atoms of carboxylate and acid amide groups. 

To get a directed coupling of a peptide via its N-terminal NH2-group, the introduction of a monochloroacetylglycyl residue during peptide synthesis is recommended. Of course, coupling via NH2-, SH-, or carboxyl groups of peptide side chains is also possible. 

As carboxylic esters of 8-hydroxyquinoline are readily hydrolyzed in the presence of metal ions, it has been possible to develop the carbo(8-quinoloxy) substituent as an amino-protecting group for peptide synthesis (Scheme 14). 

Comparison of the deduced sequence of A. saitoi carboxypeptidase with other known serine carboxypeptidase sequences shows that they share a low degree of similarity 32% with wheat carboxypeptidase II, 32.3% with malt carboxypeptidase II and 26.2% with yeast carboxypeptidase Y (Figure 19) [88], However, all of the sequences conserve the catalytic domains (indicated by boxes II to IV in Figure 19) and the domain (box I in the Figure 19) which contains the amino acid residues recognizing the C-terminal carboxylate group of peptide substrates. There are also present in the sequence ten potential sites for N-linked glycosylation. 

Electrostatic forces these include the interactions between two ionic groups of opposite charge, for example the ammonium group of Lys and the carboxyl group of Asp, often referred to as an ion pair or salt bridge. In addition, the noncovalent associations between electrically neutral molecules, collectively referred to as van der Waals forces, arise from electrostatic interactions between permanent and/or induced dipoles, such as the carbonyl group in peptide bonds. 

The fifth chapter has been mainly written by Dr Shyamal I. Parekh, who has also been responsible for all the production process in preparing the final manuscript. The general philosophy is again apparent. A new reaction was needed to manipulate the carboxyl group in peptides and in compounds... 

Sheehan and another Nobel laureate Khorana showed independently that the mild carbodiimide mediated synthesis is very useful in the condensation reaction of N-blocked amino acids with a different amino acid to form a peptide bond. The O-blocking of carboxylic acid groups in peptide synthesis with amino nucleophiles, such as glycine esters or amides, " or novel silicon containing protective groups is also mediated by carbodiimides. Likewise, alcohols are protected with 4-benzyloxybutyric acid, using EDC/DMPA. ... 

Protection of carboxyl groups. The deblocking reaction discussed above with 2 is also applicable to a halogenated protected derivative of the terminal carboxyl group of peptides. The N-protected amino acid is converted by the Passerini reaction with an o-halo aldehyde into a protected derivative such as 4. The derivative is cleaved by reiietion with 2 at 20° in acetonitrile or methanol (equation III). 

It has been reported that there are salty stimuli in peptides. Tada et al. (27) inadvertently discovered the synthesized salty dlpeptides, L-0rn-3-Ala HCl, L-Om-Tau HCl, Lys-Tau HCl and L-Orn-Gly HCl having the same intensity taste as NaCl. The salty taste of L-Orn-Tau HCl and Lys-Tau HCl was more intense than that of L-Orn-3-Ala HCl and L-Orn-Gly - HCl. The degree of dissociation of the carboxyl or sulfonyl group in peptides was assumed to contribute to the intensity of the salty taste. These dipeptides may be useful as new seasonings for diabetics and hypertensives because they contain no Na ions. 

Figure 3 Different approaches for the introduction of lipid functionalities, here exemplified via the farnesyl group, into peptides. (A) Lipidated amino acid building blocks. (B) Substitution of bromoalanine with a nucleophile. (C) Alkylation or acylation of a free thiol functionality of a cysteine. (D) Conjugate addition of a nucleophile (e.g., farnesylthiolate) to a dehydroalanine. (E) Conjugate addition of a nucleophile to aziridine-2-carboxylic acid containing...

The amino group in this structure could be an e-amino group of lysine or hydroxylysine or the terminal a-amino group of the second chain. In the latter case the /3- or 7-carboxyl peptide link would constitute a branching point rather than a cross-link. 

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