Metal Binding Properties of Fluorescent Analogues of Trichogin GA IV: A Conformational Study by Time‐Resolved Spectroscopy and Molecular Mechanics Investigations

Abstract

The metal ion binding properties of two fluorescent analogues of trichogin GA IV, which is a natural undecapeptide showing significant antimicrobial activity, were studied by circular dichroism, time-resolved optical spectroscopy, and molecular mechanics calculations. Binding of Ca(II) and Gd(III) to the peptides investigated was shown to promote a structural transition from highly helical conformations to folded structures characterized by formation of a loop that embedded the metal ion. Time-resolved spectroscopy revealed that peptide dynamics is also remarkably affected by ion binding: peptide-backbone motions slowed down to the microsecond time scale. Finally, molecular mechanics calculations emphasized the role of the central Gly5-Gly6 motif, which allowed for the twisting of the peptide segment that gave rise to the formation of the binding cavity.

The several facets of Trichogin GA IV: High affinity Tb(III) binding properties. A spectroscopic and molecular dynamics simulation study

“…We already reported similar experiments concerning the interaction of F0TrOMe with Gd(III) and Ca(II) ions, which showed the same behavior as that of Tb(III) ions . Interestingly, the titration with the Gd(III) ions produced a positive CD band very similar in shape and intensity to the corresponding band recorded for the F0TrOMe/Tb(III) ion complex.…”

“…The dynamics of a conformational transition from an elongated, helical conformation to a family of compact, folded structures, for some Trichogin analogs was characterized by us some years ago, by use of theoretical conformational analysis and time‐resolved spectroscopic studies . We have also found that in these fluorescent TrGA analogs the conformational transition from an essentially helical structure to a turn conformation may be triggered by the binding of Ca(II) and the lanthanide Gd(III) ions …”

Spectroscopically labeled peptaibiotic analogs: the 4‐nitrophenylalanine infrared absorption probe inserted at different positions into trichogin GA IV

“…According to the MD calculations, the conformation switch takes place at the level of the –Gly 5 –Gly 6 – dipeptide, already known to be fairly flexible . The lowest energy (33.72 kcal/mol) 3 D structure is shown in Figure .…”

Peptide and Protein Interaction with Membrane Systems

“…However, the MD results indicate that, in the case of trichogin, membrane thinning might be driven also by specific interactions between the peptide N-and C-termini and the phospholipid headgroups. In this respect, it is important to note that we have previously shown that in solvents of low polarity trichogin binds cations with a very high affinity [142]. This result might reflect …”

“…A well characterized, medium-length peptaibiotic is GAIV, whose sequence is nOct -Aib 1 -Gly 2 -Leu 3 -Aib 4 -Gly 5 -Gly 6 -Leu 7 -Aib 8 -Gly 9 -Ile 10 -Lol, where nOct is n-octanoyl, and Lol is leucinol. This 10-mer peptide was isolated from Trichoderma longibrachiatum in 1992 [6] and since then it was studied both in solution and in model membranes by a number of physico-chemical techniques [108] including NMR [6,54], X-ray crystallography [137], EPR [88-90, 114, 130, 131] fluorescence [45,86,126,[140][141][142] electrochemistry [10,123], and molecular dynamics (MD) simulations [17]. Its 3D-structure is helical, with a flexible hinge in the central part, formed by two consecutive Gly residues [6,137,138,141].…”