title: Analogues of cyclolinopeptide A containing alpha-hydroxymethyl amino acid residues.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry, Technical University of Łódź, Zeromskiego 116, 90-924 Łódź,Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Zubrzak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Banaś
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kaczmarek
authors.forename: Mirosław T
authors.initials: MT
authors.lastname: Leplawy
authors.forename: Marek
authors.initials: M
authors.lastname: Sochacki
authors.forename: Marek L
authors.initials: ML
authors.lastname: Kowalski
authors.forename: Barbara
authors.initials: B
authors.lastname: Szkudlińska
authors.forename: Janusz
authors.initials: J
authors.lastname: Zabrocki
authors.forename: Paola
authors.initials: P
authors.lastname: Di Lello
authors.forename: Carla
authors.initials: C
authors.lastname: Isernia
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Ettore
authors.initials: E
authors.lastname: Benedetti
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic; C055018:cyclolinopeptide A