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Accueil du site > Équipes de recherche > Chimie Organique et Médicinale > Peptoid > Thèmes de recherche > Novel peptoid-type architectures

Novel peptoid-type architectures


α,β-Peptoids

The synthesis of a novel family of peptidomimetics composed of linear and cyclic α,β-alternating peptoids was developed. Oligomers consisting of up to six peptoid residues (n = 1-3) were synthesized on large scale with use of an efficient iterative solution-phase method and longer oligomers (n = 4, 5) were obtained by the coupling of appropriately protected shorter oligomers. Preliminary conformational studies of these hybrid peptoids have been performed.

Convenient Solution-Phase Synthesis and Conformational Studies of Novel Linear and Cyclic α,β-Alternating Peptoids.
Hjelmgaard T., Faure S., Caumes C., De Santis E., Edwards A.A., Taillefumier C. Org. Lett. 2009, 11, 4100-4103.


Arylopeptoids

A highly convenient and efficient protocol for iterative solution phase synthesis of shorter oligomers of para- and meta-arylopeptoids (i.e. oligomeric N-substituted aminomethyl benzamides) was developed. Peptide coupling methods to access longer oligomers were studied and use of the new coupling reagent COMU was found to be the most efficient for creation of the tertiary benzamide bonds. The cis/trans isomerism of arylopeptoid backbones were studied by means of NMR and was found to be highly dependent on the nature of the side chains. Thus, increasing the bulkiness of the side chains would favor the cis amide bond conformation and arylopeptoids that carry tert-butyl side chains contain exclusively cis amide bonds.


Expedient Solution-Phase Synthesis and NMR Studies of Arylopeptoids.
Hjelmgaard T., Faure S., Staerk D., Taillefumier C., Nielsen J. Eur. J. Org. Chem. 2011, 4121-4132.

The solid-phase synthesis of para- and meta-arylopeptoids (oligomeric N-substituted aminomethyl benzamides) can be performed according two strategies involving a submonomer approach in which the arylopeptoid residues were created in an iterative manner on the growing chain using an acylation–substitution cycle. The first strategy involves in the acylation step, benzoic acid building blocks and the uronium salt COMU as efficient reagent for ensuring fast and clean coupling. An improved methodology was further developed using benzoyl chloride building blocks. This methodology has enabled the synthesis of arylopeptoids with tert-butyl and phenyl side chains, which allows for complete control over the amide conformation. The method has furthermore enabled the first synthesis and preliminary conformational studies of arylopeptoids bearing (S)-N-(1-phenylethyl) side chains.

Effect of capping groups at the N- and C-termini on the conformational preference of α,β-peptoids.
De Santis E., Hjelmgaard T., Caumes C., Faure S., Alexander B.D., Holder S.J., Siligardi G., Taillefumier C., Edwards A.A. Org. Biomol. Chem. 2012, 10, 1108-1122.

Improved solid-phase synthesis and study of arylopeptoids with conformation-directing side chains.
Hjelmgaard T., Faure S., De Santis E., Staerk D., Alexander B.D., Edwards A. A., Taillefumier C., Nielsen J. Tetrahedron 2012, 68, 4444-4454. (invitation, special issue of Tetrahedron (Symposium in print) on Chemistry of Foldamers).

Rapid and convenient semi-automated microwave assisted solid-phase synthesis of arylopeptoids.
Rasmussen J. E., Boccia M. M., Nielsen J., Taillefumier C., Faure S. Hjelmgaard T. Tetrahedron Lett. 2014, 55, 5940–5943.