Peptides catalysts

E. Brule, K. K. M. Hii, Y. R. de Miguel, Polymer-supported manganese porphyrin catalysts— Peptide-linker promoted chemoselectivity, Org. Biomol. Chem. 3 (2005) 1971. 

Peptide catalysts, peptides that catalyze chemical reactions such as aldol, retro-aldol, and Michael reactions. In contrast to enzymes or catalytic antibodies ( abzymes), small peptides often display limited catalytic activity and substrate specificity. Combinatorial methods combined with reaction-based or catalysis-based high-throughput selection approaches are suited for catalyst optimization [E. Tanaka, Chem. Record 2005, 5, 276]. 

Polymeric reagents and catalysts have evolved from the polymers used in ion exchange and in solid phase peptide synthesis. Most ion exchange resins are prepared by functionalization of cross-linked polystyrenes, and are used for water purification and as acidic and basic catalysts. Peptides are synthesized on similar polystyrene supports. Multistep modifications of polymers are used to produce non-commercial reagents and catalysts. However, peptide and nucleotide syntheses still provide the best-developed examples of polymeric reagents, and ion exchange resins are the most widely used polymer-supported catalysts. 

Reagents, catalysts Reagents, catalysts Reagents, catalysts Reagents, catalysts Peptide synthesis Peptide synthesis... 

Synthetic peptide dendrimers, catalytic antibodies, RNA catalysts, peptide foldamers as well as other native or modified enzymes with completely different fxmctions were discovered to catalyze carbon-carbon bond formation [15]. 4-Oxalocrotonate tau-tomerase (4-OT) catalyzes in vivo the conversion of 2-hydroxy-2,4-hexadienedioate (136) to 2-oxo-3-hexenedioate (137) (Scheme 10.33a), and it belongs to the catabolic pathway for aromatic hydrocarbons in P. putida mt-2 [200]. This enzyme carries a catalytic amino-terminal proline, which could act as catalyst in the same fashion as the proline mediated by organocatalytic reactions. Initial studies demonstrate that this enzyme was able to catalyze aldol condensations of acetaldehyde to a variety of electrophiles 138 (Scheme 10.33b) [200]. This enzyme was also examined as a potential catalyst for carbon-carbon bond forming Michael-type reactions of acetaldehyde to nitroolefins 139 (Scheme 10.33c) [201,202]. 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

Deamidation of soy and other seed meal proteins by hydrolysis of the amide bond, and minimization of the hydrolysis of peptide bonds, improves functional properties of these products. For example, treatment of soy protein with dilute (0.05 A/) HCl, with or without a cation-exchange resin (Dowex 50) as a catalyst (133), with anions such as bicarbonate, phosphate, or chloride at pH 8.0 (134), or with peptide glutaminase at pH 7.0 (135), improved solubiHty, whipabiHty, water binding, and emulsifying properties. 

For the equiUbrium-controUed enzyme-catalyzed peptide synthesis the equiUbrium position Hes far over in the direction of the hydrolysis, and under physiological conditions, the product yield is negligible. The equiUbrium position is deterrnined exclusively by thermodynamic factors and like any other catalysts the enzymes only accelerate the attainment of the equiUbrium. 

Diphenylmethyl esters are similar in acid lability to r-butyl esters and can be cleaved by acidic hydrolysis from 5-containing peptides that poison hydrogenolysis catalysts. 

H2/Pd-C. If hydrogenation is carried out in the presence of (BOC)20, the released amine is directly converted to the BOC derivative. H2/Pd-C, NH3, —33°, 3-8 h, quant.When ammonia is used as the solvent, cysteine or methionine units in a peptide do not poison the catalyst. Pd-C or Pd black, hydrogen donor, solvent, 25° or reflux in EtOH, 15 min-2 h, 80-100% yield. Several hydrogen donors, including cyclohex-... 

Synthetic organic polymers, which are used as polymeric supports for chromatography, as catalysts, as solid-phase supports for peptide and oligonucleotide synthesis, and for diagnosis, are based mainly on polystyrene, polystyrene-divinylbenzene, polyacrylamide, polymethacrylates, and polyvinyl alcohols. A conventional suspension of polymerization is usually used to produce these organic polymeric supports, especially in large-scale industrial production. 

Many individual compound reports contain infrared spectral information, but there is only one in which detailed analysis appears. The 3-hydroxytriazolopyri-dine 125 used as a catalyst for peptide coupling (Section IV.J) has been studied in the solid and in solution, in association with a crystallographic study, and shown to exist as a dimer in solution (99MI1). 

A very considerable body of work has been published on the use of 3-hydrox-ytriazolopyridine (HOAt) 280 and its derivatives as peptide coupling catalysts,... 

Murakami, Y. Functionaiited Cyclophanes as Catalysts and Enzyme Models. 115, 103-151 (1983). Mutter, M., and Pillai, V. N. R. New Perspectives in Polymer-Supported Peptide Synthesis. 106, 119-175 (1982). 

The chloromethylated polystyrene resin used for Merrifteld solid-phase peptide synthesis is prepared by treatment of polystyrene with chloromethyl methyl ether and a Lewis acid catalyst. Propose a mechanism for the reaction. 

Flynn, G.C., Chappell, T.G., Rothman, J.E. (1989). Peptide binding and release by proteins implicated as catalysts of protein assembly. Science 245, 385-390. 

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

An interesting case in the perspective of artificial enzymes for enantioselective synthesis is the recently described peptide dendrimer aldolases [36]. These dendrimers utilize the enamine type I aldolase mechanism, which is found in natural aldolases [37] and antibodies [21].These aldolase dendrimers, for example, L2Dl,have multiple N-terminal proline residues as found in catalytic aldolase peptides [38], and display catalytic activity in aqueous medium under conditions where the small molecule catalysts are inactive (Figure 3.8). As most enzyme models, these dendrimers remain very far from natural enzymes in terms ofboth activity and selectivity, and at present should only be considered in the perspective of fundamental studies. 

Figure 3.8 Aldol reaction and peptide dendrimer catalyst.

---