Solid‐phase synthesis and characterization of N ‐methyl‐rich peptides
2005; Wiley; Volume: 65; Issue: 2 Linguagem: Inglês
10.1111/j.1399-3011.2004.00213.x
ISSN1399-3011
AutoresMeritxell Teixidò, Fernando Alberício, Ernest Giralt,
Tópico(s)Carbohydrate Chemistry and Synthesis
ResumoAbstract: A library of peptides required for a project investigating the factors relevant for blood–brain barrier transport was synthesized on solid phase. As a result of the high N ‐methylamino acid content in the peptides, their syntheses were challenging and form the basis of the work presented here. The coupling of protected N ‐methylamino acids with N ‐methylamino acids generally occurs in low yield. (7‐azabenzotriazol‐1‐yloxy)‐tris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP) or PyBOP/1‐hydroxy‐7‐azabenzotriazole (HOAt), are the most promising coupling reagents for these couplings. When a peptide contains an acetylated N ‐methylamino acid at the N‐terminal position, loss of Ac‐ N ‐methylamino acid occurs during trifluoroacetic acid (TFA) cleavage of the peptide from the resin. Other side reactions resulting from acidic cleavage are described here, including fragmentation between consecutive N ‐methylamino acids and formation of diketopiperazines (DKPs). The time of cleavage is shown to greatly influence synthetic results. Finally, high‐performance liquid chromatography (HPLC) profiles of N ‐methyl‐rich peptides show multiple peaks because of slow conversion between conformers.
Referência(s)