Cytochrome P450 and temperature-induced modulation of Raman scattering


Temperature evolution of resonant Raman scattering for high-quality bilayer 2H-MoS presented encapsulated in hexagonal BN flakes. The observed resonant Raman scattering spectrum is induced by a laser energy of 1.96 eV, close to the A-exciton resonance, showing a rich and unique vibrational signature not observed in non-resonant scattering. The emergence of first- and second-order phonon modes is clearly observed over a broad temperature range from 5 to 320 K. The spectra include Raman active modes, namely E21 gram (Γ) and one 1 gram (Γ) and their Davydov splitting counterparts, namely E1u(Γ) and B1u(Γ). The temperature evolution of Raman scattering spectra brings key observations, as the integrated intensity distributions of different phonon modes show different trends. The Raman-active A1 g(Γ) mode, which dominates the Raman scattering spectrum at T = 5 K, is quenched with increasing temperature. Surprisingly, at room temperature the B1u(Γ) mode, which is IR active in the bilayer, is much stronger than its nominally Raman-active A 1 gram(Γ) counterpart.


Cytochrome P450s (CYPs) are a superfamily of heme-containing enzymes mainly expressed in the liver and play a crucial role in the oxidative biotransformation and elimination of drugs1. Among the 57 human CYPs, CYP3A4 is the most abundant type, and it is involved in the metabolism and clearance of almost half of all human CYPs. Modulation of CYP activity through drug induction or inhibition often results in clinically significant drug-drug interactions (DDIs) leading to unexpected adverse drug reactions (ADRs) or treatment failures3,4,5. In addition, severe inhibition or induction of CYP results in drug withdrawal from the market, resulting in time and financial losses. 6. To minimize DDI and reduce post-market withdrawal of drugs, effective modulation of CYP activity by an investigational drug is a necessary procedure prior to drug approval7 , 8.

Current CYP activity assessment techniques rely on end-point analysis using invasive methods, such as mass spectrometry, fluorescence, and luminescence-based activity assays 9, 10, 11 , which hinders comprehensive studies at the cellular level. Although fluorescent and luminescent probes have been developed to image CYP activity in living cells12,13,14, low biocompatibility and high cytotoxicity limit the use of most of the probes in development in living cells10 application. In addition, conventional methods assess the modulation of CYP activity by measuring catalytic products. . Other factors have been shown to affect catalytic products, such as deficiency of redox chaperones (NADPH-cytochrome P450 reductase or cytochrome b 5) 15, 16 and inhibition of drug transporters 17 . Whether the effect is directly on CYP itself or other related factors is difficult to clarify. Therefore, a molecular probe-independent method for targeting CYP enzymes would facilitate the assessment of CYP activity under the most natural conditions without concern for associated factors.

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