Soluble supports peptide

Soluble PEG supports have been used for different applications such as the synthesis of peptides (241, 245) and peptidomimetics (246) soluble-supported catalysts (247-249), reagents (250-253), scavengers (254), and traceless linkers (255-257) to improve purification protocols (258, 259) and high-loading PEG-derived soluble supports (260), particularly in the synthesis of arrays of small organic molecules (261-275). Several recent reviews (276-281) illustrate their usefulness but also show how additional efforts could make PEG liquid-phase combinatorial synthesis more reliable. 

While PEG-based supports are widely used for liquid-phase combinatorial chemistry, other non-PEG-based soluble polymers have also been reported for combinatorial applications. A recent review (276) contains an exhaustive list of homo- and copolym-eric soluble supports used in peptide, oligonucleotide, and oligosaccharide synthesis, including combinatorial chemistry. Two of these supports have also been used for small organic molecule synthesis. Homopolymeric polyvinyl alcohol was used in conjunction with PEG for a protection/derivatization strategy in solution (284), and the copolymer between isopropylacrylamide and acrylic acid was used in the catalytic hydrogenation of a Cbz group (285). 

The principal difference between the synthesis of individual peptides and peptide libraries is that mixtures of amino acids, rather than individual amino acids, are incorporated into selected or all positions of the sequence of peptide libraries. However, all current peptide chemistry strategies can be used for the synthesis of peptide libraries. In general, library synthesis requires greater emphasis on simplicity and reproducibility of the synthesis process. Although soluble supports have also been used for peptide library synthesis,the majority of methods used to synthesize peptide combinatorial libraries utilize Merrifield s concept of solid-phase synthesis,which is based on the sequential assembly of peptides after covalent attachment of the C-terminal amino acid to a polymeric solid support. This enables the excess of reagents to be removed by simple wash and filtration processes, and avoids the... 

Shemyakin et al. tried to eliminate the steric complications encountered in solid-phase peptide synthesis by using linear, non-crossiinked polystyrene of molecular weight 200000 as a soluble support for the growing peptide chain. All coupling and... 

The answer to the former problem came once again from peptide synthesis, when Bayer and coworkers [309] reported the first use of polyethylene glycol) (PEG) as a soluble support for peptide synthesis. The idea was immediately picked up by Koster, who prepared a PEG-20000 terminating in a dimethoxytrityl linker (Figure 19.16) and demonstrated the attachment of thymidine [310]. Later, Bayer and coworkers [311] assembled up to a pentanucleotide by the phosphodiester method on a PEG-NH2 support with a phosphoramidate linker cleavable by isoamyl... 

All synthetic peptide libraries can be classified into two main categories peptide libraries bound to a solid support (solid-support peptide libraries) and soluble... 

Ionic liquid-mediated peptide synthesis (ILMPS), peptide synthesis using ionic liquids as non-conventional media or soluble support. The application of ionic liquids as non-aqueous reaction media in... 

In addition to dendrimers, hyperbranched polymers have been used by several groups as soluble supports for catalysts [7, 17]. These supports are polydisperse and randomly branched, and, since they are prepared in a single reaction step, are generally much cheaper materials. Nevertheless, it has been shown that catalysts immobilized on hyperbranched polymers may possess similar properties as dendritic systems [18]. Therefore, dendritic catalysts serve as ideal model systems for catalysts attached to hyperbranched polymers. We functionalized several hyperbranched polyethyleneimines (PEIs) employing the peptide coupling protocol in reactions with the pyrphos linker system. The pyrphos-rhodium complexes bound to the hyperbranched polymers were also found to be active catalysts for the hydrogenation ofZ-methyl-a-acetamidocinnamate [16]. As observed for the... 

A polymer support specially designed for cysteine-containing peptides was suggested by Glass et al [92]. They prepaid a support from PEG and 4-phenoxy-3,5-dinitro-benzoyl chloride with a capacity of 0.1-0.2 mmolg" This soluble support reacts rapidly and selectively with the sidechain sulfhydryl groups of cysteine in aqueous buffers at pH 7. Hius, polymer-bound peptides are obtained with a thiolsensitive dinitrophenylene link which permits an easy release of peptides from the polymer ... 

Polymer-supported small peptides as well as the B-chain of bovine insulin were reported to be soluble in water and in some organic scdvents when using PEG derivatives with a molecular mass of 6000gmol to this purpose. Enzymatic investigations showed that this linear soluble support does not restrict the access of enzymes to bound peptides. 

Soluble supports (W = 6000 g mol ) of the following structure have been used with 4-<2-nitrovinyl)benzoic acid as terminal group (loading capacity 86%) [93]. The loading capacity of the latter POE-derivative was 75% (0.25 mmol g ). Such solubilizing polymer-based protecting groups are of considerable interest for the synthesis of cysteine peptides. 

The optimum loading capacity was suggested as being about 0.5 mmolg" because a higher degree of substitution would not be favorable by reason of a reduced solubility of the polymer-supported peptide. Noteworthy are the refinements on the purification procedure of the polymer support According to... 

---