Analogues of cyclolinopeptide A containing a-hydroxymethyl amino acid residues.

Linear and cyclic cyclolinopeptide A (CLA) analogs contg. a-hydroxymethyl-leucine (HmL) in positions 1, 4, and 1 & 4, and a-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 examd. for their immunosuppressive activity in the lymphocyte proliferation assays (LPA). Only HmL-contg. peptides demonstrated at about 25% lower immunosuppressive activity, but they are four times more sol. in water solns. 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 soln., at room temp. in CDCl3, and the conformation compared with that obsd. for CLA in the solid state.