Recognition Polymers

From the universe of polymeric materials which appear in biology and medicine we select for discussion that set whose principal function is to recognize and respond appropriately to specific substances in their environment. They may be 1.2, 2.2, or 3 dimensional shapes such as messenger RNA, cellulose acetate membranes, or artificial esophagi. They may function by recognizing the difference between right and wrong chemical species and responding by binding the correct ones and rejecting the wrong ones, e.g., enzymes and their substrates, codons and their anticodons. What happens after recognition and response is not of interest at the moment, e.g., the catalytic effect of the enzyme on the bound substrate or the codonanticodon binding effect on protein synthesis.

Another example is in the chemical senses where there is sketchy evidence that proteins are involved in recognizing tastants. This could be done by having a protein on the tongue bind all tastants (rather close contact is required to make fine distinctions) and then recognize them by very intimate contacts and sending signals to the brain for conscious recognition. Alternatively, each taste modality may have a protein that excludes all but one type and generates only one signal for the CNS.

Another important class are antibodies that recognize their own antigens out of about 10⁴ different ones and complex with them and exclude the others. A model for antigen-antibody interaction must account for the non-binding of nonantigens as well as the much simpler case of the binding of the antigen.

Another class are the permselective membranes that recognize some species and let them pass while recognizing others and not let them pass. A final class to be discussed will be implant polymers which have an un-desired ability to recognize and bind platelets.

The question we are asking is whether it is possible to establish general principles in chemical physics that govern these different types of molecular recognition so that the principles could be incorporated into polymer design. Recent advances in “intermolecular” force theory suggests that this goal is achievable in the foreseeable future. Intermolecular has been put in quotes because when two molecules are in sufficiently close contact to recognize one another they probably have an appreciable exchange term and are therefore not two molecules but one.

The recent advances referred to involve computer simulation of complex formation using the new 1-4-6-12 potential forms corresponding to a long range (R^?1) coulombic electrostatic interaction, a medium range (R^?4) electrostatic-induced dipole attraction, a short range (R^?6) dispersive attraction, and a very short range (R^?12) orbital overlap repulsion. In the cases of interest, e.g., in an aqueous environment, all four terms are important and statements such as “the binding is purely electrostatic,” i.e., all R^?1, are misleading as well as wrong (since even ions need the R^?12 repulsion to keep them at their equilibrium distance). Discussions of permeability in terms of “pore sizes” is equally limiting for it implies that only the R^?12repulsion is appreciable. The fallacy of using competitive equilibria to determine the relative contributions of terms will be discussed. The im: portant use in biology of “other contacts” within the system to give a variable base line so that the typical binding-no binding discrimination can be made with attraction-less attraction rather than the more awkward attraction-repulsion potentials will also be discussed.