Introduction of functional groups into peptides via N-alkylation.
An optimized protocol for the mild and selective Fukuyama-Mitsunobu reaction was used for mono- and di- N-alkylation on solid support. Thereby, nonfunctionalized aliphatic and aromatic residues are quickly introduced into transiently protected, primary amines of a linear peptide. N-Alkylation can also be used to implement alkyl chains carrying (protected) functionalities suited for subsequent modification. Applicability of this method is demonstrated by various N-alkylated analogues of a cyclic CXCR4 receptor antagonist originally developed by Fujii et. al.
Demmer
O
O
Department Chemie, Lehrstuhl II für organische Chemie, Technische Universität München, Lichtenbergstrasse 4, D-85747 Garching, Germany.
Dijkgraaf
I
I
Schottelius
M
M
Wester
H-J
HJ
Kessler
H
H
D000478:Alkylation; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors
D000588:Amines; D008024:Ligands; D010455:Peptides; D019718:Receptors, CXCR4