Abstract:Modification of the drug excited state properties within proteins provides information on binding and may result in a different photoreactivity.
“…In homogeneous aqueous solutions of PSA or chlorin the 1 O 2 lifetime has been determined as 3.5 µs, in accordance with the data reported for other photosensitizers [38]; such a low value reflects efficient quenching of singlet oxygen by water molecules. In the presence of HSA, however, the two examined systems behave quite differently; cf.…”
Section: Transient T-t Absorbance Of Psa and Singlet Oxygen Emissionmentioning
“…In homogeneous aqueous solutions of PSA or chlorin the 1 O 2 lifetime has been determined as 3.5 µs, in accordance with the data reported for other photosensitizers [38]; such a low value reflects efficient quenching of singlet oxygen by water molecules. In the presence of HSA, however, the two examined systems behave quite differently; cf.…”
Section: Transient T-t Absorbance Of Psa and Singlet Oxygen Emissionmentioning
“…12 Stereodifferentiation in the triplet lifetimes of ligands within transport proteins has previously been observed in other cases, such as carprofen, flurbiprofen, flurbiprofen methyl ester or 2-anthracene propionic acid incorporated into serum albumins. 7c,14
…”
“…160 ms) was more than 500 times longer than that obtained for 3 COL* in acetonitrile (s ¼ 0.29 ms), which agrees well with the markedly longer triplet lifetimes usually measured in the intraprotein microenvironment. 43,44,63 Comparison of the decay traces of 3 COL* in acetonitrile and 3 COL*@TU in aqueous solutions revealed that the initial intensity of the signal immediately aer the laser pulse was higher in the organic solvent (Fig. 1, inset).…”
Section: Resultsmentioning
confidence: 99%
“…42 More recently, laser ash photolysis (LFP) has been introduced as a new tool to investigate drug-protein interactions and to determine binding parameters such as affinity constants or population of the binding sites. 43,44 Interestingly, the absence of a triplet excited state detectable in LFP has revealed that COL does not bind to serum albumins. 45 This technique is very sensitive and does not require separation of free and complexed drug.…”
Colchicine (COL) is a bioactive molecule with antitumor properties. When COL binds to tubulin (TU), it inhibits microtubule assembly dynamics. We have investigated COL-TU interactions using laser flash photolysis (LFP) technique and performing fully flexible molecular dynamics simulations. Excitation of COL at 355 nm in aqueous medium did not lead to any transient absorption spectrum. By contrast, in the presence of TU a transient peaking at l max ca. 420 nm was registered and assigned as triplet excited COL complexed with TU ( 3 COL*@TU). In aerated medium, the lifetime was s ca.160 ms and the quantum yield was 0.138. Likewise, when the bicyclic COL analog MTC was submitted to LFP in the presence of TU, 3 MTC@TU* was detected with a lifetime of ca. 62 ms and a quantum yield of 0.296, Aqueous solutions of MTC did not produce any signal in the microsecond timescale. The triplet energy of MTC was obtained by means of emission measurements and found to be ca. 200 kJ mol À1 , a value that matches with that previously reported for COL (188 kJ mol À1 ).Molecular dynamic simulations, both with the ground and triplet excited state, reveal a strong interaction between COL and TU to give stabilized complexes with restricted mobility inside the protein binding site. These results demonstrate that LFP is a useful methodology to study the binding of COL derivatives to TU and open a new way to evaluate the interactions of nonfluorescent anticancer drugs with this protein.
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