Introduction of the maleimide function onto resin-bound peptides: a simple, high-yield process useful for discriminating among several lysines.
Incorporation of epsilon-Adpoc-lysine as a residue in solid phase peptide synthesis allows selective deprotection of this residue on the resin-bound peptide relative to other acid labile groups such as Boc. Premature resin cleavage is avoided. A maleimide group, a useful thiol-capture reagent, was readily introduced by reacting the liberated amino function with an acylating agent containing the maleimide functionality. Acidic cleavage from the resin, with an appropriate scavenging system, afforded peptides that are derivatized with a maleimide functionality on a specific lysine. This is advantageous for producing peptide-carrier conjugates of defined specificity, useful as immunogens, by maleimide-thiol coupling. The derivatization and resin removal chemistries appear to proceed in excellent yield with respect to the maleimide group. The structures were confirmed by tandem mass spectrometry.
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
S
S
Marburg
A C
AC
Neckers
P R
PR
Griffin
D007987:Gonadotropin-Releasing Hormone / Q000138:chemical synthesis; D008239:Lysine; D008301:Maleimides / Q000737:chemistry*; D013058:Mass Spectrometry; D010455:Peptides / Q000138:chemical synthesis*; D012116:Resins, Plant
D008301:Maleimides; D010455:Peptides; D012116:Resins, Plant; C043592:maleimide; D007987:Gonadotropin-Releasing Hormone; D008239:Lysine