Peptides Schiff base-activated

H Gausepohl, U Pieles, RW Frank. Schiff base analog formation during in situ activation by HBTU and TBTU, in JA Smith, JR Rivier, eds. Peptides Chemistry and Biology. Proceedings of the 12th American Peptide Symposium, Escom, Leiden, 1992, pp 523-524. 

Dissolve the required amount of peptide (1 mole peptide per about 50 moles of lysine residues of the carrier, e.g., 60 pmol of peptide per 5 mg ovalbumin) in PBS and mix with the activated carrier. Stir at RT for 1 h and block with 10 mg/ml of solid NaBH4 at RT for 20 min. Alternatively, reduce (block) the formed azome-thines (Schiff bases) to secondary amines by addition of ascorbic acid (final concentration 5 mM). 

Aminocyclopropanecarboxylic acid (74) has attracted special interest (a) as a modified model of natural a-amino acids, in the synthesis of bioactive peptide analogs, potential enzyme inhibitors , or e.g. a derivative with sweetness receptor activity s and (b) together with its Schiff-base metal complexesas the biosynthetic precursor of ethene, the plant ripening hormone . (See these sources and the review in Reference 135 for further references.)... 

The manifold important zinc-containing biological systems have spawned a multitude of model complexes,thereby greatly enriching knowledge of the coordination chemistry of zinc (see Sections 8 and 9). Types of model complexes include those with amino acid ligands to model zinc-peptide interactions, NNN-donor ligands to model the active site of carbonic anhydrase or carboxypeptidases, NO-donor Schiff bases to model Zn2 sites, and and polynuclear... 

The presence of pyridoxal phosphate confers specific absorbance properties onto the holoenzyme. The absorption maximum is at 330 mp, a wavelength far removed from that of the Schiff base. Therefore, the combination of apoenzyme and coenzyme in the active phosphorylase molecule does not involve the formation of a Schiff base. Krebs and others studied the site of attachment of the phosphorus in the phosphorylase molecule by preparing P-labeled phosphorylase. After the enzyme was treated with trypsin, it became clear that the phosphorus was present in a basic hexa-peptide containing two basic amino acids. The hexa-peptide has the following amino acid sequence lysine, glutamine, isoleucine, serine phosphate, valine, and arginine. 

Another family of chiral ligands useful in catalyzing ACA to a variety of substrates in conjunction with CuOTf consists of the peptide-based arylphosphine Schiff bases. These modular ligands can be easily modified structurally in order to fine tune their catalytic activity as a function of the substrate. Thus, while cyclopen-tenone generally reacts poorly with alkylzinc reagents, especially (r-Pr)2Zn, optimization studies permitted development of a chiral peptide ligand which allows ACA of these two entities with 94% yield and 85% ee (eq 102). ... 

One reaction type that merits special consideration is the acylation of amino acids. Other reactions of the amino acids are biologically important. For example, it will be seen later that it is Schiff base formation of the amino function with an aldehyde that provides the basis for all reactions with vitamin (see Chapter 7). However, it is acylation of the amino function of one amino acid with the carboxyl (activated) of another amino acid that leads to formation of the peptide bond and subsequent protein, or polymer formation. It then becomes of interest for the bioorganic chemist to consider and compare the synthesis of the most complex macromolecule in the test tube and the organism. 

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