Solid-phase synthesis of C-terminally modified peptides.

In this paper, a straightforward and generic protocol is presented to label the C-terminus of a peptide with any desired moiety that is functionalized with a primary amine. Amine-functional molecules included are polymers (useful for hybrid polymers), long alkyl chains (used in peptide amphiphiles and stabilization of peptides), propargyl amine and azido propyl-amine (desirable for 'click' chemistry), dansyl amine (fluorescent labeling of peptides) and crown ethers (peptide switches/hybrids). In the first part of the procedure, the primary amine is attached to an aldehyde-functional resin via reductive amination.

Synthesis of alkyne-bridged cyclic tripeptides toward constrained mimics of vancomycin.

The synthesis of a range of highly constrained cyclic tripeptides has been performed using either an intramolecular Sonogashira coupling or a macrolactamization as the final ring-closing reaction. Our approach gives access to rigidified 15-membered peptidic macrocycles based on the central ring system of vancomycin. Tripeptides 3a-c and dipeptide 11 were cyclized via an intramolecular Sonogashira reaction, and the cyclic peptides 4a-c and 15a were obtained in 6-23% yield.

Ring-closing metathesis for the synthesis of side chain knotted pentapeptides inspired by vancomycin.

A versatile method for the synthesis of bicyclic side chain knotted peptides inspired by vancomycin is described. The synthetic approach is based on the incorporation of a central amino acid derivative having two allylic groups-introduced by a Stille coupling-into pentapeptide 8 containing two allylated serine residues. Treatment of this bis-ring-closing metathesis precursor with 2nd generation Grubbs catalyst results in the formation of a bicyclic pentapeptide with the correct side chain to side chain connectivity pattern as observed in vancomycin: i- 2 --> i, i --> i + 2.