Solid-phase synthesis of peptides

Burke TR Jr, Smyth M, Nomizu M, Otaka A, Roller PP. Preparation of fluoro- and hydroxy-4-(phosphonomethyl)-D,L-phenylalanine suitably protected for a solid-phase synthesis of peptides containing hydrolytically stable analogues of O-phosphotyrosine. J Org Chem 1993 58 1336-1340. 

Matsueda GR, Stewart JM. A p-methylbenzhydrylamine resin for improved solid-phase synthesis of peptides amides. Peptides 1981 2 45-50. 

Solid-Phase Synthesis of Peptides with Triazolides and Imidazolides... 

A-Acetylimidazole was found to be a very efficient terminating (capping) agent in the solid-phase synthesis of peptides.t40],[41] A terminating agent is used to block any N-terminal amino groups that have not reacted in the coupling steps.[40]... 

Monaghan, Sean, Griffith-Johnson, David, Matthews, Ian and Bradley, Mark (2001). Solid-phase synthesis of peptide-dendrimer conjugates for an investigation of integrin binding. Arkivoc, 2001, (Part (x)), 46-53. http //eprints.soton.ac.uk/19576/... 

Kaiser E, Colescott RL, Bossinger CD, Cook PI (1970) Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem 34 595-598... 

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... 

FIGURE 5.4 Schematic representation of a continous-flow system for the solid-phase synthesis of peptides. Solvent is forced through the system by a pump. The support is in the form of a column that is stationary. A reaction is monitored by measuring the change in absorbance of the solvent stream. 

GR Matsueda, J Stewart. A p-methylbenzhydrylarnine resin for improved solid-phase synthesis of peptide amides. Peptides 2, 45, 1981. 

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. 

With the development of appropriate cartridges and proper chemistry that would allow the synthesis of the molecule on the disk and than the use of the same disk directly for affinity chromatography by placing it in a chromatographic cartridge, it is reasonable to expect that SMC will become a very efficient tool in the solid phase synthesis of peptides, oligonucleotides, and similar molecules. 

A linker originally designed for solid-phase synthesis of peptides is the backbone amide linker (11) (BAL), this anchoring approach has now been extended to the combinatorial synthesis of diverse amide [31], hydroxamate [32], oligosaccharide [33] and heterocyclic small molecule libraries [34-36]. 

Continuous reactions at the side chains of branched or comblike structured polymers play an important role in the solid-phase synthesis of peptides or oli-go-nucleotides. 

P. Wipf, T.C. Henninger, Solid-phase synthesis of peptide mimetics with ( )-alkene amide bond replacements derived from alkenylaziridines, J. Org. Chem. 62 (1997) 1586-1587. 

Songster, M. F. Vagner, J. Barany, G. Acid-Labile Handles for Fmoc Solid-Phase Synthesis of Peptide V-Alkylamides, Lett. Pept. Sci. 1995, 2, 265. 

R. Bruce Merrifield Chemistry Solid-phase synthesis of peptides... 

An alternative solid-phase synthesis of peptide thioamides that uses methyl dithioesters to introduce the sulfur involves addition of DMAP and cesium trifluoroacetate. 24 These additives greatly accelerate the thioamide-forming reaction and give low levels of racemi-zation according to Marfey s test analysis 25 of an Alaip[C(=S)—NH]Val product. 

Nitro- or 2,4-dinitrobenzenesulfonamides of primary or secondary amines can be hydrolyzed under mildly basic conditions, and are increasingly being used for amine protection (see Section 10.1.10.7 [123,139,140]). /V-(2-Nitrobenzenesulfonyl)amino acids can be used as an alternative to TV-Fmoc amino acids for the solid-phase synthesis of peptides [141]. Deprotection is achieved by treatment of the polystyrene-bound sulfonamide with a solution of PhSH (0.5 mol/L) and K2C03 (2 mol/L) in DMF for 10 min at room temperature [141], conditions that do not lead to cleavage of esters (e.g. of the Wang linker) or to racemization. The condensation of polystyrene-bound sulfinamides H2N-SO-Pol with aldehydes yields /V-sulfinylimines, which add... 

Phthalimide protection is stable towards acids and bases, but can be cleaved with strong nucleophiles, such as hydrazines or sulfides, or by reduction with sodium boro-hydride [230]. More sensitive towards nucleophilic attack than unsubstituted phthalimide is tetrachlorophthalimide [33]. This group has been successfully used as N(a) protection of amino acids in the solid-phase synthesis of peptides (deprotection N2H4/DMF (15 85), 40 °C, 1 h coupling DIC/HOAt/amino acid (1 1 1), 3 equiv. of each, DMF, 25 °C, 4 h [294]). Typical conditions for the removal of phthaloyl protection on cross-linked polystyrene include treatment of the resin with hydrazine hydrate [295,296], with methyl hydrazine [297], or with primary aliphatic amines [298] in DMF, EtOH, or solvent mixtures for several hours at room temperature or above [296,299,300]. Illustrative examples are sketched in Figure 10.15. It has been claimed that the hydrazinolysis of polystyrene-bound phthalimides proceeds more readily in DCM or DCE than in DMF [301]. 

One of the major tools in combinatorial chemistry has been rooted in the ingenious solid-phase synthesis of peptides by Merrifield.1... 

In this chapter we consider Fmoc solid-phase synthesis of peptide analogs containing the amide surrogate that tend to be isosteric with the natural amide. This includes synthesis of peptidosulfonamides, phosphonopeptides, oligoureas, depsides, depsipeptides, and peptoids. 

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