title: Antimicrobial lipopeptaibol trichogin GA IV: role of the three Aib residues on conformation and bioactivity.
abstract: The lipopeptaibol trichogin GA IV is a natural, non-ribosomally synthesized, antimicrobial peptide remarkably resistant to the action of hydrolytic enzymes. This feature may be connected to the multiple presence in its sequence of the non-coded residue α-aminoisobutyric acid (Aib), which is known to be responsible for the adoption of particularly stable helical structures already at the level of short peptides. To investigate the role of Aib residues on the 3D-structure and bioactivity of trichogin GA IV, we synthesized and fully characterized four analogs where one or two Aib residues are replaced by L-Leu. Our extensive conformational studies (including an X-ray diffraction analysis) and biological assays performed on these analogs showed that the Aib to L-Leu replacements do not affect the resistance to proteolysis, but modulate the bioactivity of trichogin GA IV in a 3D-structure related manner.
authors.affiliation: ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131, Padova, Italy. marta.dezotti@unipd.it
authors.forename: Marta
authors.initials: M
authors.lastname: De Zotti
authors.forename: Barbara
authors.initials: B
authors.lastname: Biondi
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Park
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Hahm
authors.forename: Marco
authors.initials: M
authors.lastname: Crisma
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
mesh_terms: D019943:Amino Acid Substitution; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007700:Kinetics; D007930:Leucine / Q000737:chemistry; D055666:Lipopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014250:Trichosporon / Q000187:drug effects / Q000254:growth & development; D014961:X-Ray Diffraction
chemical_list: D000621:Aminoisobutyric Acids; D000890:Anti-Infective Agents; D055666:Lipopeptides; C116419:trichogin GA IV; C100049:2-aminoisobutyric acid; D007930:Leucine