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.
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.
Albericio
F
F
Department of Chemistry, University of Minnesota, Minneapolis.
van Abel
R
R
Barany
G
G
D000596:Amino Acids; D001216:Asparagine; D004126:Dimethylformamide; D005449:Fluorenes; D005973:Glutamine; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis*; D011384:Proinsulin / Q000138:chemical synthesis; D013935:Thymic Factor, Circulating / Q000138:chemical synthesis; D014269:Trifluoroacetic Acid; D014631:Valerates
D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D014631:Valerates; D005973:Glutamine; C064395:5-(4-(9-fluorenylmethyloxycarbonyl)aminomethyl-3,5-dimethoxyphenoxy)valeric acid; D001216:Asparagine; D004126:Dimethylformamide; D011384:Proinsulin; D013935:Thymic Factor, Circulating; D014269:Trifluoroacetic Acid