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Isothermal Titration Calorimetry
TLDR
In this unit several protocols are presented, ranging from the basic ones aimed at characterizing binding of moderate affinity to advanced protocols that are aimed at determining very high or very low affinity binding processes. Expand
Characterization of protein-protein interactions by isothermal titration calorimetry.
TLDR
This methods chapter is devoted to describing protein-protein interactions, in particular, the association between two different proteins and the self-association of a protein into homodimers. Expand
Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes
TLDR
The enzymatic characterization of HIV-1 proteases with sequences found in drug-naïve Ugandan adults points to a higher biochemical fitness of the A and C proteases in the presence of existing inhibitors. Expand
Isothermal titration calorimetry to determine association constants for high-affinity ligands
TLDR
Isothermal titration calorimetry (ITC) can be used to determine the complete binding thermodynamics of a ligand down to the picomolar range by using an experimental mode called displacement titration. Expand
Identification of pharmacological chaperones as potential therapeutic agents to treat phenylketonuria.
TLDR
2 small molecules are identified that may represent promising alternatives in the treatment of PKU and significantly increased activity and steady-state PAH protein levels in cells transiently transfected with either WT-PAH or PKU mutants. Expand
The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design.
TLDR
The results indicate that the effectiveness of this inhibitor against the resistant mutant is related to two factors: extremely high affinity against the wild type achieved by combining favorable enthalpic and entropic interactions, and a mild effect of the protease mutation due to the presence of flexible structural elements at critical locations in the inhibitor molecule. Expand
Overcoming drug resistance in HIV‐1 chemotherapy: The binding thermodynamics of Amprenavir and TMC‐126 to wild‐type and drug‐resistant mutants of the HIV‐1 protease
TLDR
Analysis of the data for TMC‐126 and KNI‐764, another second‐generation inhibitor, indicates that their low susceptibility to mutations is caused by their ability to compensate for the loss of interactions with the mutated target by a more favorable entropy of binding. Expand
Amplification of the effects of drug resistance mutations by background polymorphisms in HIV-1 protease from African subtypes.
TLDR
A complete thermodynamic dissection of the differences between proteases from different subtypes and the effects of the V82F/I84V drug-resistant mutation within the framework of the B, C, and A subtypes is presented. Expand
HIV-1 protease inhibitors: enthalpic versus entropic optimization of the binding affinity.
TLDR
Tripeptide inhibitors derived from the transframe region of Gag-Pol (Glu-Asp-Leu and Glu- asp-Phe) bind to the HIV-1 protease with a favorable enthalpy change, qualitatively different from that of known inhibitors and points to new strategies for inhibitor design. Expand
Thermodynamic basis of resistance to HIV-1 protease inhibition: calorimetric analysis of the V82F/I84V active site resistant mutant.
TLDR
The predominantly enthalpic effect of the V82F/I84V mutation is consistent with the idea that the introduction of the bulkier Phe side chain at position 82 and the Val side chain in position 84 distort the binding site and weaken van der Waals and other favorable interactions with inhibitors preshaped to the wild-type binding site. Expand
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