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Solid-phase synthesis of peptides with C-terminal asparagine or glutamine. An effective, mild procedure based on N alpha-fluorenylmethyloxycarbonyl (Fmoc) protection and side-chain anchoring to a tris (alkoxy) benzylamide (PAL) handle

Albericio, F.; van Abel, R.; Barany, G.

International Journal of Peptide and Protein Research 35(3): 284-286

1990

ISSN/ISBN: 0367-8377
PMID: 2354880
Accession: 041390491
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Attempts to anchor Fmoc-asparagine or glutamine as p-alkoxybenzyl esters for solid-phase peptide synthesis are fraught with difficulties. A convenient and effective method to prepare peptides with C-terminal asparagine or glutamine involves quantitative attachment of N alpha-Fmoc-C alpha-tert.-butyl aspartate or glutamate via the free omega-carboxyl groups to a tris(alkoxy)benzylamino (PAL) support. Chain elongation proceeds normally by standard Fmoc chemistry, and treatment with acid, e.g., CF3COOH--CH2Cl2, 90 min at 25 degrees, releases the desired peptides in greater than 95% yields without side reactions at the C-terminus. Feasibility of the approach has been demonstrated by the syntheses of the C-terminal octapeptide from human proinsulin, H-Leu-Ala-Leu-Glu-Gly-Ser-Leu-Gln-OH, and the serum thymic factor pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH.

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Related References

Albericio, F.; Abel, R.V.; Barany, G. 1990: Solid-phase synthesis of peptides with C -terminal asparagine or glutamine : An effective, mild procedure based on N x-fluorenylmethyloxycarbonyl (Fmoc) protection and side-chain anchoring to a tris(alkoxy)benzylamide (Pal) handle Chemical Biology and Drug Design 35(3): 284-286
Han, Y.; Solé, N.A.; Tejbrant, J.; Barany, G. 1996: Novel N omega-xanthenyl-protecting groups for asparagine and glutamine, and applications to N alpha-9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis Peptide Research 9(4): 166-173
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