Solution phase peptide synthesis

Watts, P., Wiles, G., Haswell, S. J., PoMBO-ViLiAR, E., Solution phase synthesis of f-peptides using micro reactors. Tetrahedron 58, 27 (2002) 5427-5439. 

Watts P, Wiles C, Haswell SJ, Pombo-ViUar E, Styring P (2001) The Synthesis of Peptides Using Microreactors. Chem Comm 11 990-991 Watts P, Wiles C, Haswell S, Pombo-Villar E (2002a) Investigation of Racemi-sation in Peptide Synthesis within a Microreactor. Lab Chip 2 141-144 Watts P, Wiles C, Haswell S, Pombo-Villar E (2002b) Solution Phase Synthesis of Beta-Peptides Using Microreactors. Tetrahedron 58 5427-5439... 

The solution phase synthesis of peptides often results in mixtures of labelled, unlabelled compounds along with other impurities and requires extensive purification. A route using a solid phase approach [polyethylene glycol-poly-styrene PEG-PS derivatised with a xanthen-2-oxovalerate (XAL) linker] was recently developed [193] (Scheme 44). 

In general, solid-phase synthesis, rather than solution-phase synthesis, can be the preferred method for the generation of combinatorial libraries because of the greater abihty to automate a solid-phase protocol, primarily due to the use of excess reagents in solution to effect cleaner reactions and to the ease of workup by simple filtration. The solid-phase method of peptide synthesis has had many notable successes. However, the preparation of peptides containing more than 20 amino acids in length using the solid-phase technique often causes major problems in that very extensive purification of the final product is needed. 

Boc-Based Solution-Phase Synthesis of Phosphoserine and Phosphothreonine Peptides... 

During the early part of this decade, most efforts in high-throughput synthesis utilized solid phase organic synthesis (SPOS) techniques.1-3 SPOS was a natural outgrowth of earlier methods used to synthesize peptides and oligonucleotides.4 This method has several advantages over traditional solution-phase synthesis ... 

Catalytic hydrogenation of peptides containing a Phe(4-N02) residue, to be subsequently converted into Phe(4-N3), that also contain cystine and/or methionine residues, requires extended reaction times. This may lead to desulfuration. Therefore, a Phe(4-NH2) residue is used as a precursor for Phe(4-N3) in the synthesis of AVP to give Phe(4-N3) residues at either position 2 or 3.1281 In this solution-phase synthesis, the 4-amino group in the 4-amino-... 

Scheme 45 Solution-Phase Synthesis of Peptides Incorporating Nucleo Alanines 83-86 ...

The synthesis of the Saa-peptide conjugates in solution follows standard solution-phase synthesis using, for example, IIDQt117 or EDC as the coupling agent. The reaction is checked by TLC (ninhydrin and/or 10% H2S04 in MeOH dip). The product is usually purified by flash chromatography. 

Incorporation of a-Saal by solution-phase synthesis, used to demonstrate its influence on the conformation of a linear peptide, has been performed for the Leu-enkephalin analogue H-Tyr-a-Saal-Phe-Leu-OMe (59) in which the Saa replaces the Gly-Gly dipeptide segment of the natural sequence H-Tyr-Gly-Gly-Phe-Leu-OH (Scheme 9).[45 ... 

Fragment coupling method was first applied to glycopeptide 11 (Scheme 3). The C-terminal peptide 12 was prepared by traditional solution-phase synthesis, while the activated -terminal glycopeptide 13 was prepared by solution-phase synthesis with solid-phase workup as described. The coupling between 12 and 13 was achieved in NMP and the product was readily isolated by precipitation. Target glycopeptide 11 was obtained in 89% overall yield (28). 

The final step in the solution-phase synthesis is to deprotect the N terminus of the completed peptide. The N-terminal amide bond must be cleaved without breaking any of the peptide bonds in the product. Fortunately, the benzyloxycarbonyl group is partly an amide and partly a benzyl ester, and hydrogenolysis of the benzyl ester takes place under mild conditions that do not cleave the peptide bonds. This mild cleavage is the reason for using the benzyloxycarbonyl group (as opposed to some other acyl group) to protect the N terminus. 

Q Show how you would use solution-phase synthesis or solid-phase synthesis to make a given peptide. Use appropriate protecting groups to prevent unwanted couplings. Q Discuss and identify the four levels of protein structure (primary, secondary, tertiary, and quaternary). Explain how the structure of a protein affects its properties and how denaturation changes the structure. Problems 24-44, 45, and 52... 

The 9-fluorenylmethoxycarbonyl group is another distinguished contribution from the Carpino laboratory198199 to the solution-phase synthesis of peptides and latterly it has been adapted to solid-phase peptide synthesis too.200 The Fmoc group is exceptionally stable towards acid thus, carboxylic acids can be converted to acid chlorides with thionyl chloride201 or terf-butyl esters using sulfuric acid and isobutene.202 Furthermore, Fmoc groups are unscathed by HBr in... 

Figure 4 Sequences of lipidated peptides discussed in this review. The frizzled lines Indicate the building blocks used for the block coupling strategy of the solution-phase synthesis (when applicable). Abbrevations BiotAca N-(+)-Biotinyl-6-aminocaproyl MantAca N-methylanthranyl-6-aminocaproyl MIC 6-Maleimidocaproyl NBDAca N-(4-nitrobenz-2-oxa-l, 3-diazol-7-yl)-6-aminocaproyl.

Gastrins and gastrin analogs have drawn great interest from chemists, and many total synthesis studies have been reported. Solution-phase synthesis was achieved by Anderson et al. in the 1960s (10). In 1980, Brown and coworkers reported a solid-phase synthesis of these two peptide amides... 

The solution-phase synthesis and resolution of new phosphinopeptidic building blocks containing a triple bond and their involvement in 1,3-dipolar cycloaddition with a variety of in j// -prepared nitrile oxides allowed the diastereoselective preparation of a novel class of isoxazole-containing phosphinic peptides 619. Inhibition assays of some of these peptides revealed their behavior as very potent inhibitors of metalloproteases, outmatching previously reported phosphinic peptides in terms of potency <2003CEJ2079>. 

Zhang, W. (2004) Fluorous tagging strategy for solution-phase synthesis of small molecules, peptides and oligosaccharides. Curr. Opin. Drug Discov. Develop., 7, 784—797. 

The practicability of catalyst 2 has been demonstrated in the synthesis of peptide aldehydes libraries targeting caspases 1 and 3 [12], The peptide aldehydes were prepared using a succession of solid phase, and polymer-assisted solution phase synthesis, and were obtained in excellent purity. 

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