From competition to cooperation: a highly efficient strategy towards well-defined (co)polypeptides

Abstract

By associating primary (slow but controlled ring-opening polymerization; ROP) and tertiary (fast but uncontrolled ROP) amines in the same molecule, a novel highly active organocatalytic system proceeding by an accelerated amine mechanism through monomer activation (AAMMA) and leading to living ROP of α-amino acid N-carboxyanhydrides at room temperature was successfully developed.

Synthesis of polypeptides via bioinspired polymerization of in situ purified N -carboxyanhydrides

“…The interfacial anchoring of macroinitiators is not the only way to achieve fast kinetics for SIMPLE polymerization. An enhanced polymerization rate was also reported in solution phase when initiators are properly designed (25,38). When the DCM solution of polynorbornene-derived, brush-like initiators (PNB) (25) was added into a DCM/water biphasic system containing nonpurified BLG NCAs ( Fig.…”

“…In addition, polypeptides with tunable MWs were also obtained with Tris(2-aminoethyl)amine as the initiator, which exhibited fast polymerization kinetics due to the activation of NCA monomers (SI Appendix, Fig. S14) (38). To validate that the rapid polymerization kinetics is critical to minimize water-induced side reactions, control polymerizations were carried out in the presence of 1-pyrenemethyl amine without a rate acceleration mechanism.…”

Polypeptide‐Based Conjugates as Therapeutics: Opportunities and Challenges

“…Additionally, ROP of NCAs renders polypeptides with conserved N‐terminal ends and can be used to introduce functionalities at the C‐terminal site for latter conjugation strategies. Synthetic aspects of polypeptide production are outside of the scope of this review and can be found elsewhere …”

Primary ammonium/tertiary amine-mediated controlled ring opening polymerisation of amino acid N-carboxyanhydrides

“…15 Also primary/tertiary amine organocatalytic systems have been introduced promoting an accelerated amine mechanism through monomer activation (AAMMA). 16 Ammonium salts are attractive alternatives to amines as initiators for ROP of NCAs as they are more stable, easier to handle and to purify. Schlaad et al 13 postulated that the ammonium-mediated ROP mechanism may involve an equilibrium between dormant (ammonium) and active (amine) o-chain ends (Scheme 1c), leading to a controlled propagation like in living cationic polymerisation or nitroxide-mediated radical polymerisation.…”