Dimerization tripeptides

Das AK, Banerjee A, Drew MGB, Haidar D, Baneijee A. Stepwise self-assembly of a tripeptide from molecular dimers to supramolecular /8-sheets in crystals and amyloid-like fibrlis in the solid state. Supramol Chem 2004 16 331-335. 

Lipases are also known to catalyze amide formation. Thus in 1987 Margolin and Klibanov [40] showed the use of porcine pancreatic lipase (PPL) for dipeptide synthesis in organic solvents. West and Wong [41] investigated several lipases and esterases for dipeptide and tripeptide synthesis, with variable yields observed. Later, Kawashiro et al. [42] also studied the dimerization of phenylalanine with PPL. 

Sheehan and co-woricers prepared a pentapeptide, L-Thr-L-Ala-L-Ser-L-His-L-Asp as an esterase model, from a viewpoint that three amino acids (serine, histidine and aspartic acid) are involved at the active site 131,132). The rate constant for the pentapeptide if, 1.5 sec (pH 7.73,25.5°) is greater than 0.25 M sec for tripeptide L-Gly-L-His-L-Ser and 0.3 M sec for imidazole. Not much rate enhancement was observed also for the cyclic dimer of the tripeptide. Subsequently, they conducted the solvolysis of an amino acid derivative 70 by oligopeptides, 11 and L-Ser-7-aminobutyl-L-His-7-aminobutyl-L-Asp72. 

Figure 5 Comparison of thioredoxin coupled arsenate reductase (pI258 family) and glutaredoxin coupled arsenate reductase (R773 family). GSH reduced glutathione, the tripeptide consisting of y-glutamyl-cysteine-glycine. GSSG S-S bridged oxidized dimer of glutathionine.

Phe, D-Phe and D-Phe ierf-butyl ester. The enzyme was not active toward L-Phe methyl ester, (L-Phe)2 methyl ester, (L-Phe)4, Boc-(L-Phe)4, Boc-(L-Phe)4 methyl ester, (D-VaDa, (D-Leu)2, or (D-Ala)n (n = 2 - 5). These properties indicated that the enzyme is an endopeptidase that acts D-stereospecifically upon peptides composed of aromatic D-amino acids. On the other hand, a dimer was formed when D-Phe methyl ester and D-Phe amide were the substrates. Eight stereoisomers of Phe trimer were synthesized, and their effectiveness as substrates for the enzyme was tested. The enzyme recognized the configuration of the second D-Phe of tripeptides and catalyzed the hydrolysis of the second peptide bond from the N-terminus. The calculated Vmax/Km values for the peptides containing L-Phe were lower than that for (D-Phels, affected by the configuration of the neighboring L-Phe. The enzyme also showed P-lactamase activity toward ampicillin and penicillin G. The calculated Vmax values of the enzyme for b-lactam compounds were about the same as those for (D-Phe)3 and (D-Phe)4, while the Km values were several hundred times larger. On the other hand, carboxypeptidase DD and D-aminopeptidase activities were undetectable. 

Fig. 2 (a) Dimeric / -sheet assembly formed by cyclo[(L-Phe-D- A-Ala-L-Leu-D- A-Ala)2-]. For clarity, stick drawings were used for heavy atoms in the side chains, (b) Alignment of dipoles by stacking cyclic tripeptides built from 6-amino acids. (From Ref. [16].)... 

A Chloroacetyl chloride was reacted in aqueous alkaline solution with glycylglycine, obtained from diketopiparazine. After ammonolysis the tripeptide was esterified with methanolic HCl. The ester (1) on melting yielded the dimeric hexapetide ester that was saponified to hexaglycine. 

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