Solid-phase-bound peptide

Epoxidation of enones with short solid-phase bound peptides [10.2]... 

Gausepohl, H. and Behn, C. (2002) Automated synthesis of solid-phase bound peptides. In Peptide Arrays on Membrane Support, eds. J. Koch and M. Mahler, pp. 55-68. Berlin Springer-Verlag. 

Scheme 8. Asymmetric enone epoxidation with solid-phase bound peptide catalysts.

Catalytic activity was observed when a 625-membered undecapeptide library was complexed with Zr(IV). Beads with active catalysts were easily identified under a low-power microscope and the structures of the active peptides were analyzed by Edmann degradation. The activity of four Zr(IV)-peptide complexes was further proven and quantified in solution-phase experiments not only with the examined indigo derivative but also with the corresponding para-nitrophenyl phosphate. The group extended the screening for phosphodiesterase activity and enabled discovery of solid phase bound peptide-Eu3+ complexes as hydrolyzing agents [15]. 

Berkessel A, Gasch N, Glaubitz K, Koch C (2001) Highly enantioselective enone epoxidation catalyzed by short solid phase-bound peptides. Org Lett 3 3839-3842... 

Scheme 16. Monodisperse and solid-phase-bound peptide catalysts for the Julia-Colonna epoxidation.

BerkerseF s group has used short solid-phase bound peptides for the epoxidation of enones (Scheme 12.20). The reaction was performed with H2O2 and NaOH as base in CH2CI2 [137]. The authors observed that with longer peptide sequences better ee s were achieved. Maximum ee values were found with 5 units, although with only modest yield (34%) (Scheme 12.20). 

Berkessel A, Koch B, Toniolo C, Rainaldi M, Broxterman QB, Kaptein B (2006) Asymmetric enone epoxidation by short solid-phase bound peptides further evidence for catalyst helicity and catalytic activity of individual peptide strands. Biopolymers 84 90-96... 

While all syntheses originally presented had been based on the strategy of coupling the biomolecule to a prochelator, a different approach has been presented by Peterson et al. (1999). This new way uses a solid phase bound peptide as anchor to build the chelator step by step (O Fig. 45.16). Solid phase synthesis offers many advantages one of the major advantages is that by-products may simply be washed away from the solid phase while the desired product stays bound. 

DIRECT SOLID-PHASE GLYCOSYLATION OF SOLID-SUPPORT-BOUND PEPTIDES 273... 

An example of catalysts which are themselves heterogeneous are the poly-amino acids used for the asymmetric Julia-Colonna-type epoxidation of chalcones using alkaline hydrogen peroxide (Section 10.2) [8]. Because of the highly efficient synthesis of epoxides, this process also has attracted industrial interest (Section 14.3). Since recent work by the Berkessel group revealed that as few as five L-Leu residues are sufficient for epoxidation of chalcone, several solid-phase-bound short-chain peptides have been used, leading to enantioselectivity up to 98% ee [14], For example, (L-Leu)5 immobilized on TentaGel S NH2 , 8, was found to be a suitable solid-supported short-chain peptide catalyst for epoxidations. 

In addition, solid-phase bound short-chain peptides have been recently found by the Ber-kessel group to act as highly efficient catalysts in asymmetric epoxidation reactions [17]. In the early 1980s, Julia and Colonna reported that chalcone 11 can be epoxidized asymmetrically by akaline hydrogen peroxide in the presence of poly-amino acids as catalysts [18, 19], The work by Berkessel et al. revealed that in fact as little as five I-Leu residues are sufficient for the epoxidation of the enone 11 with 96-98% ee (Scheme 8). 

During solid phase synthesis peptides are bound to the solid support by means of the C-terminal carboxyl group. The properties of the anchor group positioned between the growing oligomer and the solid support are crucial for the success of a solid phase synthesis. Usually, specialised linkers are used which provide either peptide carboxylic acids or peptide carboxylic amides upon cleavage [4]. A cleavage mechanism that proceeds by a nucleophilic attack... 

Despite the biological significance of the triazole moiety and the success of intermolecular triazole formation, intramolecular alkyne-azide couphng remains surprisingly Hmited. On a macromolecular scale, intramolecular triazole formation can occur on specially synthesized DNA molecules [93] by cyclodimerization of solid-phase bound suitably functionalized peptides [94] or on copper surfaces to induce adhesion [95]. There are just a few traditional examples on macrocycloadditions [96-98]. 

In contradiction to this, the protein biosynthesis proceeds via aminolysis of activated amino acids reactively bound to t-RNA, where the growing protein is liberated from the polymer RNA support (Fig. 3). This type of biosynthesis was imitated in the way of a drastically simplified model reaction, namely the peptide syntheses with solid phase bound activated amino acid esters [37, 38], which here are not the matter for discussion (Fig. 4). 

The choice of a linker/anchor compound determines the fate of the peptide products. Stable amide/ester bonds such as with the Ala- Ala spacer Protocol 3) result in an array of immobilized peptides. Conventional linker chemistry can be incorporated to yield cleavable peptides in different formats. Esterification reactions are problematic in this open reactor system in such cases, a preformed amino add linker compound should be used. Such linkers should allow a solid phase bound deprotection/pre-purification followed by a mild final release reaction. Several options have been described (23-25). More sophisticated and superior amino membranes are now available from several sources (ABIMED, AIMS, Jerini, PerSeptive). 

Kilbum and coworkers studied solid-phase-bound tweezer receptors that contain peptide arms linked through... 

Berkessel et al. addressed the question of identifying the minimal catalophore (i.e., the minimum peptide length for catalytic activity). For this purpose, they synthesized a library of L-leu oligomers (1-20 mer) on TentaGel, and tested these solid-phase-bound oligopeptides in the Julia-Colonna epoxidation [38]. This work revealed that as few as five L-Leu residues are sufficient for the epoxidation of chalcone to take place with 96-98% enantiomeric excess. The result strongly suggests that one turn of a helical peptide is the minimal structural element required for catalysis. 

The investigation of minor groove-binding polyamides was greatly accelerated by the implementation of solid-phase synthesis [48]. Originally demonstrated on Boc-y9-Ala-PAM resin with Boc-protected monomers, it was also shown that Fmoc chemistry could be employed with suitably protected monomers and Fmoc-y9-Ala-Wang resin (Fig. 3.8) [49]. Recently, Pessi and coworkers used a sulfonamide-based safety-catch resin to prepare derivatives of hairpin polyamides [50]. Upon activation of the linker, resin-bound polyamides were readily cleaved with stoichiometric quantities of nucleophile to provide thioesters or peptide conjugates. 

The solid phase parallel synthesis of tetrahydroim idazo[ 1,2-a] [ 1,3,5J tri azep i n-2-thiones and 2-imines has been reported starting from resin-bound peptides <06JCO127>. Pyrazolo[T,5 l,6]pyrimido[4,5-cfjpyridazinones with potent and selective phosphodiesterase 5 (PDEj) inhibitory activity have been described <06JMC5363>... 

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