Preparation of the very acid-sensitive Fmoc-Lys(Mtt)-OH. Application in the synthesis of side-chain to side-chain cyclic peptides and oligolysine cores suitable for the solid-phase assembly of MAPs and TASPs.
N alpha-9-Fluorenylmethoxycarbonyl-N epsilon-4=methyltrityl-lysine, [Fmoc-Lys(Mtt)-OH], was prepared in two steps from lysine, in 42% overall yield. The N epsilon-Mtt function can be quantitatively removed upon treatment with 1% TFA in dichloromethane or with a 1:2:7 mixture of acetic acid/trifluoroethanol/dichloromethane for 30 min and 1 h at room temperature, respectively. Under these conditions, groups of the tert-butyl type and peptide ester bonds to TFA-labile resins, such as the 2-chlorodiphenylmethyl- and the Wang-resin, remained intact. The utility of the new derivative in peptide synthesis has been exemplified with the synthesis of a cyclic cholecystokinin analog. As an example of further application, five types of lysine cores suitable for the solid-phase synthesis of one, two or three epitopes containing antigenic peptides or template-assembled synthetic proteins have been synthesized on Merrifield, Wang and 2-chlorodiphenylmethyl resin.
Aletras
A
A
Department of Chemistry, University of Patras, Greece.
Barlos
K
K
Gatos
D
D
Koutsogianni
S
S
Mamos
P
P
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D000939:Epitopes / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D014320:Triphenylmethyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry*
D000939:Epitopes; D005449:Fluorenes; C096179:N(alpha)-9-fluorenylmethoxycarbonyl-N(epsilon)-4-methyltrityllysine; D010456:Peptides, Cyclic; D014320:Triphenylmethyl Compounds; D008239:Lysine