Biological activity, hydrophobic

Aguilar, M.B., Lezama-Monfil, L., Maillo, M., Pedraza-Lara, H., Lopez-Vera, E., and Heimer de la Cotera, E.P. (2006) A biologically active hydrophobic T-1-conotoxins from the venom of Conus spurius. Peptides, 27, 500-505. 

The work by Hammett and Taft in the 1950s had been dedicated to the separation and quantification of steric and electronic influences on chemical reactivity. Building on this, from 1964 onwards Hansch started to quantify the steric, electrostatic, and hydrophobic effects and their influences on a variety of properties, not least on the biological activity of drugs. In 1964, the Free-Wilson analysis was introduced to relate biological activity to the presence or absence of certain substructures in a molecule. 

The first use of QSARs to rationalise biological activity is usually attributed to Hansc [Hansch 1969]. He developed equations which related biological activity to a molecmle electronic characteristics and hydrophobicity. For example ... 

Protein tertiary structure is also influenced by the environment In water a globu lar protein usually adopts a shape that places its hydrophobic groups toward the interior with Its polar groups on the surface where they are solvated by water molecules About 65% of the mass of most cells is water and the proteins present m cells are said to be m their native state—the tertiary structure m which they express their biological activ ity When the tertiary structure of a protein is disrupted by adding substances that cause the protein chain to unfold the protein becomes denatured and loses most if not all of Its activity Evidence that supports the view that the tertiary structure is dictated by the primary structure includes experiments m which proteins are denatured and allowed to stand whereupon they are observed to spontaneously readopt their native state confer matron with full recovery of biological activity... 

In addition to chemical derivatives, purity of hGH must also be established with respect to physically associated forms. The hydrophobically linked, noncovalent dimer of hGH found to exhibit relatively low biological activity (21) is present at a level of 1—2% ia most hGH preparations at the time of... 

Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

In HIC, the hydrophobic interactions are relatively weak, often driven by salts in moderate concentration (I to 2 M), and depend primarily on the exposed residues on or near the protein surface preservation of the native, biologically active state of the protein is an important feature of HIC. Elution can be achieved differentially by decreasing salt concentration or increasing the concentration of polarity perturbants (e.g., ethylene glycol) in the eluent. 

Hydrophobization of Polyanionic Polymers to Achieve Higher Biological Activity... 

We modified polyanionic polymers by use of a grafting reaction of hydrophobic groups onto the polymers. After an extensive evaluation for the affinity of the hy-drophobically modified (hydrophobized) polymers to cell membrane, the immuno-stimulating activity of polymers was investigated by in vitro or ex vivo experiments. Consequently, the increased biological activity was found in the hydrophobized polymer, indicating that... 

Thus, the biological activity of a drug molecule could be expressed as a function of its electronic, hydrophobic, and steric properties, and one or more such factors as hydrogen bonding or polarizability (x) which might be involved. 

One approach is to extend the columns of a measurement table by means of their powers and cross-products. An example of such non-linear PCA is discussed in Section 37.2.1 in an application of QSAR, where biological activity was known to be related to the hydrophobic constant by means of a quadratic function. In this case it made sense to add the square of a particular column to the original measurement table. This procedure, however, tends to increase the redundancy in the data. 

Electrochemical study of biologically active compounds at the O/W interface provides information on physiochemical properties of the compounds at the O/W interface and in the O and W phases or, in short, hydrophobicity or lipophilicity of biologically active compounds, which seems essential to understand their biological effects, including mode of action, structure-activity relationship, delivery, and others. 

The native, biologically active form of a protein molecule is held together by a delicate balance of noncovalent forces hydrophobic, ionic, van der Waals interactions, and hydrogen bonds. In addition,... 

---