Aiming at restricting the conformational freedom of tryptophan-containing peptide ligands, we designed a THBC (tetrahydro-β-carboline)-DKP (diketopiperazine)-based peptidomimetic scaffold capable of arranging in an unusual α-turn conformation. The synthesis is based on a diastereoselective Pictet–Spengler condensation to give the THBC core, followed by an intramolecular lactamization to complete the tetracyclic THBC-DKP fused ring system. The presence of conformers bearing the intramolecular thirteen-membered hydrogen bond that characterizes the α-turn structure is confirmed by 1H NMR conformational studies. To the best of our knowledge, this scaffold represents one of the rare examples of a designed constrained α-turn mimic.

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure / F. Airaghi, A. Fiorati, G. Lesma, M. Musolino, A. Sacchetti, A. Silvani. - In: BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1860-5397. - 9(2013), pp. 147-154. [10.3762/bjoc.9.17]

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

F. Airaghi
Primo
;
A. Fiorati
Secondo
;
G. Lesma;M. Musolino;A. Sacchetti
Penultimo
;
A. Silvani
2013

Abstract

Aiming at restricting the conformational freedom of tryptophan-containing peptide ligands, we designed a THBC (tetrahydro-β-carboline)-DKP (diketopiperazine)-based peptidomimetic scaffold capable of arranging in an unusual α-turn conformation. The synthesis is based on a diastereoselective Pictet–Spengler condensation to give the THBC core, followed by an intramolecular lactamization to complete the tetracyclic THBC-DKP fused ring system. The presence of conformers bearing the intramolecular thirteen-membered hydrogen bond that characterizes the α-turn structure is confirmed by 1H NMR conformational studies. To the best of our knowledge, this scaffold represents one of the rare examples of a designed constrained α-turn mimic.
α-turn; Conformational analysis; Diketopiperazine; Peptidomimetics; Tetrahydro-β-carboline
Settore CHIM/06 - Chimica Organica
2013
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/225837
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