Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Solvation of protein surface charges plays an important role for the protonation states of titratable surface groups and is routinely incorporated in low dielectric protein models using surface accessible areas. For many-body protein simulations, however, such dielectric boundary methods are rarely tractable and a greater level of simplification is desirable. In this work, we scrutinize how charges on a high dielectric surface are affected by the nonpolar interior core of the protein. A simple dielectric model, which models the interior as a low dielectric sphere, combined with Monte Carlo simulations, shows that for small, hydrophilic proteins the effect of the low dielectric interior is largely negligible and that the protein (and solution) can be approximated with a uniform high dielectric constant equal to that of the solvent. This is verified by estimates of titration curves and acidity constants for four different proteins (BPTI, calbindin D(9k), ribonuclease A, and turkey ovomucoid third domain) that all correlate well with experimental data. Furthermore, the high dielectric approximation follows as a natural consequence of the multipole expansion of the potential due to embedded protein charges in the presence of the low dielectric core region.
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PMID:Implications of a high dielectric constant in proteins. 1758 Oct 83

Protein therapeutics hold increasing interest with the promise of revolutionizing the cancer treatment by virtue of a potent specific activity and reduced adverse effects. Nonetheless, the therapeutic efficacy of anticancer proteins is highly compromised by multiple successive physiological barriers to protein delivery. In addition, concurrent elimination of bulk tumor cells and highly tumorigenic cancer stem-like cells (CSCs) as a promising strategy has been evidenced to significantly improve cancer therapy. Here we show that a hierarchically assembled nanocomposite can self-adaptively transform its particulate property in response to endogenous tumor-associated signals to overcome the sequential barriers and achieve an enhanced antitumor efficacy by killing CSCs and bulk tumor cells synchronously. The nanoassemblies preferentially accumulate in tumors and dissociate under tumor microenvironmental acidity accompanied by the extracellular release of small-sized ribonuclease A (RNase A)-encapsulated nanocapsule (R-rNC) and small-molecule anti-CSC doxycycline (Doc), which exhibit increased tumor penetration and intracellular accumulation. The endocytosed R-rNC rapidly releases RNase A within both CSCs and tumor cells at intracellular reductive conditions, causing cell death by catalyzing RNA degradation, while Doc eradicates CSCs by inhibiting the mitochondrial biogenesis. The hierarchical assemblies show enhanced cytotoxicity on the CSC-enriched MDA-MB-231 mammospheres and an enhanced antitumor efficacy on the xenograft tumor mouse model.
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PMID:Hierarchical Nanoassemblies-Assisted Combinational Delivery of Cytotoxic Protein and Antibiotic for Cancer Treatment. 2954 98