Inhibition of ribonuclease by copolymers of glutamic acid and aromatic amino acids.

The inhibitory influence of various acidic macromolecules on the enzymatic activity of bovine pancreatic ribonuclease has been studied extensively in recent years. Heparin (l-5) as well as other sulfated polysaccharides (5-7)) synthetic polysaccharide macroanions (8, 9), polyphloretin phosphate (4, lo), polyxenyl phosphate (ll), and acidic polymers related to humic acids (12) are among the inhibitors that have been investigated. Vandendriessche (4) observed that poly-n-aspartic acid, lie other acidic polymers, inhibited the activity of ribonuclease (4). The addition of poly-n-ornithine reversed the inhibition. In all of the above cases, the interaction of the inhibitors with ribonuclease was of an electrostatic character, in which the polyanionic macromolecules reacted with an oppositely charged protein. It is the purpose of the present investigation to elucidate in what way the presence of amino acids such as tyrosine or phenylalanine in a copolymer with an acidic amino acid would influence the inhibitory capacity toward RNase. The experiments described below indicate that the copolymer of tyrosine and glutamic acid studied is a much more efficient inhibitor of RNase than polyaspartic acid, and that in this case the attachment to the enzyme occurs not only through electrostatic interactions but also through short range urea-labile bonds.