Peptide synthesis, polymerization solid phase

Synthesis of Peptide, There is continual progress in the improvement of instruments and reagents for peptide synthesis, especially "solid phase polymerization" (90) (see Proteins). This method is suitable for the synthesis of peptides with 20 30 amino acid units. 

Combinatorial chemistry evolved from the field of solid state peptide synthesis in which peptides are prepared on a polymeric solid phase support. Such supports are traditionally composed of polymeric resin beads on to which the synthesis of a peptide is undertaken in a stepwise fashion with each amino acid being added sequentially to the peptide chain (Figure 15.1). In order to avoid the formation of side products each... 

Interesting new block copolymers are accessible through the combination of peptides prepared by solid phase synthesis or polypeptides prepared by polymerization of the corresponding A-carboxyanhydride with other polymers. The different methods for NCA synthesis and their combination with methods for preparing mostly flexible coil polymers have been reviewed. Among the numerous synthetic... 

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. 

Peptide synthesis requires the use of selective protecting groups. An N-protected amino acid with a free carboxyl group is coupled to an O-protected amino acid with a free amino group in the presence of dicydohexvlcarbodi-imide (DCC). Amide formation occurs, the protecting groups are removed, and the sequence is repeated. Amines are usually protected as their teit-butoxy-carbonyl (Boc) derivatives, and acids are protected as esters. This synthetic sequence is often carried out by the Merrifield solid-phase method, in which the peptide is esterified to an insoluble polymeric support. 

The polymeric resin used for Merrifield solid-phase peptide synthesis (Section 26.8) is prepared by treating polystyrene with iV-(hydroxymethyl) phthalimide and trifluoromethanesulfonic acid, followed by reaction with hydrazine. Propose a mechanism for both steps. 

Peptide synthesis was amenable to solid-phase techniques since the process was repetitive. The C-terminal amino acid is attached to polymeric surface and the peptide chain is assembled via a two-step process coupling of the incoming amino acid that has the alpha-amino group protected... 

The synthesis of some multiblock copolymers was attempted by successive polymerization using this iniferter technique. However, pure tri- or tetrablock copolymers free from homopolymers were not isolated by solvent extraction because no suitable solvent was found for the separation. In 1963, Merrifield reported a brilliant solid-phase peptide synthesis using a reagent attached to the polymer support. If a similar idea can be applied to the iniferter technique, pure block copolymer could be synthesized by radical polymerization. The DC group attached to a polystyrene gel (PSG) through a hydrolyzable ester spacer was prepared and used as a PSG photoiniferter (Eq. 53) [186] ... 

In conclusion, the BAL method is a novel and general strategy for solid-phase synthesis of peptides and peptide derivatives, is compatible with a wide range of functionalized polymeric supports, and is readily generalizable to other nitrogen-containing molecules.9... 

H Kunz, B Dombo. Solid phase synthesis of peptides and glycopeptides on polymeric supports with allylic anchor groups. Angew Chem Int Edn Engl 27, 711, 1988. 

The solid-phase synthesis of dendritic polyamides was explored by Frechet et al. [49]. Inspired by the technique used by Merrifield for peptide synthesis, the same strategy was used to build hyperbranched polyamides onto a polymeric support. The idea was to ensure the preservation of the focal point and to ease the purification between successive steps. The resulting polymers were cleaved from the solid support, allowing ordinary polymer characterization. The reaction was found to be extremely sluggish beyond the fourth generation. 

New allylic anchors as the HYCRAM (19) (hydroxycrotonylamide) [50] and HY-CRON (21) (hydroxycrotyl-oligoefhylene glycol-n-alkanoyl) [51] linker have been developed, which exhibit excellent properties for the solid-phase synthesis of protected peptides and glycopeptides. A more flexible spacer was inserted in the HY-CRON (21) linker between the anchor and the polymeric support in order to facilitate an efficient access to the Pd(0) complex during the detachment reaction. 

Scheme 24 Solid-Phase Synthesis of a Ferrocenyl-Modified Peptide and Its Use as NCA Polymerization Initiator 1...

Combustion (elemental) analysis of polymeric supports has mainly been used to determine the amount of halogens, nitrogen, or sulfur present in samples of cross-linked polystyrene (see, e.g., [54]). This information can be used to estimate the loading of a support, or, for example, to verify that the displacement of a halide has proceeded to completion. In solid-phase peptide synthesis, nitrogen determination has been used to estimate the loading of the first amino acid [55]. 

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