Analogues of cyclolinopeptide A containing alpha-hydroxymethyl amino acid residues.
Linear and cyclic cyclolinopeptide A (CLA) analogues containing alpha-hydroxymethylleucine (HmL) in positions 1, 4, and 1&4, and alpha-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 CDCl3, and the conformation compared with that observed for CLA in the solid state.
Zubrzak
Paweł
P
Institute of Organic Chemistry, Technical University of Łódź, Zeromskiego 116, 90-924 Łódź,Poland.
Banaś
Agnieszka
A
Kaczmarek
Krzysztof
K
Leplawy
Mirosław T
MT
Sochacki
Marek
M
Kowalski
Marek L
ML
Szkudlińska
Barbara
B
Zabrocki
Janusz
J
Di Lello
Paola
P
Isernia
Carla
C
Saviano
Michele
M
Pedone
Carlo
C
Benedetti
Ettore
E
D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013816:Thermodynamics
D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic; C055018:cyclolinopeptide A