RANDOMNESS AND BIOSPECIFICITY - RANDOM COPOLYMERS ARE CAPABLE OF BIOSPECIFIC MOLECULAR RECOGNITION IN LIVING SYSTEMS

Biospecific molecular recognition in living systems is known to be bas ed on the lock and key principle as proposed by Emil Fischer. Based on this concept, biospecific polymers have been produced synthetically b y attaching biospecific 'keys' to the polymer chain. We postulate that biospecificity can be achieved by alternative means, namely random su bstitution of a preformed polymer with suitable chemical groups or ran dom copolymerization of suitable functional monomers. Such polymers, w e suggest, will contain arrangements of the chemical functions which m imic natural biospecific sites and the probability of occurrence of su ch arrangements will depend on the average composition of the polymer. In support of this principle, we have developed several functional ra ndom copolymer systems which possess a variety of biological propertie s depending on the type of chemical function. Examples are: polymers p ossessing anticoagulant properties similar to those of heparin; polyme rs which interact specifically with components of the immune system; a nd polymers which, in contact with cells, affect their growth and meta bolism. In the case of statistical copolymers possessing 'DNA-like' pr operties obtained by phosphorylation of hydroxylated polystyrene deriv atives, Monte Carte simulations were used to determine the distributio n of phosphodiester (PDE) groups along the chains and to compute the p robabilities of occurrence of particular arrangements of PDE found in the 'DNA-like' sites. The results showed that these sites are made up of PDE groups separated by distances that closely match those between the same groups along a generatrix of the DNA double-helix cylinder. T hese findings offer the prospect of manufacturing polymeric biomateria ls endowed with biomimetic character. Moreover, they provide the basis for a hypothesis regarding the appearance of biospecificity at the or igin of life, suggesting that biospecific structures may have evolved by natural selection from purely random copolymers. It is likely there fore that biospecificity is a continuous function of randomness, arisi ng from purely statistical distributions of reactivity and evolving in to precisely defined structures such as those involved in ligand-recep tor interactions. (C) 1998 Published by Elsevier Science Limited. All rights reserved.