On-resin head-to-tail cyclization of cyclotetrapeptides: optimization of crucial parameters. |
| |
Authors: | Maria C Alcaro Giuseppina Sabatino Jacques Uziel Mario Chelli Mauro Ginanneschi Paolo Rovero Anna M Papini |
| |
Affiliation: | Dipartimento di Chimica Organica Ugo Schiff, Università di Firenze, and CNR-ICCOM, Polo Scientifico, 1-50019 Sesto Fiorentino (FI), Italy. |
| |
Abstract: | Cyclotetrapeptides are constrained cyclic peptides whose synthesis is considered a difficult task. A methodology based on on-resin head-to-tail cyclization by anchoring the side chain of a trifunctional amino acid was investigated. A series of model cyclotetrapeptides containing the RGD sequence cyclo(Xaa-Arg-Gly-Asp) (Xaa = Ala, Phe, Phg, D-Ala, D-Phe, D-Phg) was synthesized with no cyclodimerization by-products. An evaluation and optimization study of all of the parameters directly involved in the ring closure was performed. |
| |
Keywords: | Arg‐Gly‐Asp sequence cyclization cyclotetrapeptide solid‐phase synthesis |
|
|