Linear and cyclic cyclolinopeptide A (CLA) analogues containing α-hydroxymethyl-leucine (HmL) in positions 1, 4, and 1&4, and α-hydroxymethylvaline (HmV) in position 5, were synthesized by the solid-phase peptide strategy and cyclized with the 1-Ethyl-3-(3- dimethylaminopropyl)-carbodiimide/1-hydroxy-7-azabenzotriazole (EDC/HOAt) reagent. The peptides were examined for their immunosuppressive activity in the lymphocyte proliferation assays (LPA). Only HmL-containing peptides demonstrated at about 25% lower immunosuppressive activity, but they are four times more soluble in water solutions than the native CLA. It seems from the LPA results that peptide [(HmL4)CLA] is the most promising for further studies. This peptide was characterized in solution, at room temperature in CDCl 3, and the conformation compared with that observed for CLA in the solid state. © 2004 Wiley Periodicals, Inc.
Analogues of cyclolinopeptide A containing alpha-hydroxymethyl amino acid residues
ISERNIA, Carla;
2005
Abstract
Linear and cyclic cyclolinopeptide A (CLA) analogues containing α-hydroxymethyl-leucine (HmL) in positions 1, 4, and 1&4, and α-hydroxymethylvaline (HmV) in position 5, were synthesized by the solid-phase peptide strategy and cyclized with the 1-Ethyl-3-(3- dimethylaminopropyl)-carbodiimide/1-hydroxy-7-azabenzotriazole (EDC/HOAt) reagent. The peptides were examined for their immunosuppressive activity in the lymphocyte proliferation assays (LPA). Only HmL-containing peptides demonstrated at about 25% lower immunosuppressive activity, but they are four times more soluble in water solutions than the native CLA. It seems from the LPA results that peptide [(HmL4)CLA] is the most promising for further studies. This peptide was characterized in solution, at room temperature in CDCl 3, and the conformation compared with that observed for CLA in the solid state. © 2004 Wiley Periodicals, Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
