On-resin head-to-tail cyclization of cyclotetrapeptides: optimization of crucial parameters.
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.
Alcaro
Maria C
MC
Dipartimento di Chimica Organica Ugo Schiff, Università di Firenze, and CNR-ICCOM, Polo Scientifico, 1-50019 Sesto Fiorentino (FI), Italy.
Sabatino
Giuseppina
G
Uziel
Jacques
J
Chelli
Mario
M
Ginanneschi
Mauro
M
Rovero
Paolo
P
Papini
Anna M
AM
D003500:Cyclization; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D014320:Triphenylmethyl Compounds
D009842:Oligopeptides; D010456:Peptides, Cyclic; D014320:Triphenylmethyl Compounds; C047981:arginyl-glycyl-aspartic acid