Reversible inhibition of enzymes by interaction with synthetic polysaccharide macroanions

Inhibition of Lysozyme by Some Copolymers of Amino Acids*

“…Natural macromolecular enzyme inhibitors have been described (Herriott, 1941; Laskowski and Laskowski, 1954), and for the action of some of them an initial polyeleetrolytic interaction of oppositely charged enzyme and inhibitor molecules has been postulated (Green and Work, 1953). Studies on the inhibition of basic enzyme molecules with polyanions and of acidic enzyme molecules with polycations have been reported (for literature see, e.g., Coleman and Edelhoch, 1956;Mora and Young, 1959; Sela and Katchalski, 1959). Polyeleetrolytic synthetic polypeptides have served on several occasions as model compounds in these investigations (Katchalski et al, 1954;Vandendriessche, 1956;Sela and Katchalski, 1959;Komguth and Stahmann, 1960;Sela, 1962).…”

Metabolism of Drugs with Inhibition of Enzymes

“…The peptide protease inhibitors that are designed are very essential drugs. Inhibition of the enzyme is kept activated for angiotensin and hence precludes the vasoconstriction for making the blood pressure low [26].…”

Synthetic Polysaccharides. IV. Preparation of Carboxyl Derivatives of Polyglucose

“…For example, low concentrations of the polyglucose carboxyl derivatives inhibited lysozyme; this inhibition was reversed with protamine or with salts. 3 Similarly, they inhibited the depolyirerizing activity of ribonuclease but did not affect the activity of the enzyme on uridine-2':3'-(cyclic) that the polyglucose derivatives block the attachment of the bacteriophage to T-2 E. coli. The derivatives have also been used for in vivo detoxification of basic macromolecules, for example, polymyxin-B, and it was shown that the effectivity in detoxification increased with the charge density of the polyanionic derivatives.14 The activity of ACTH in vivo was increased by carboxylpolyglucose.16 Details of the biological experiments, and of the effect of differences in charge density upon them, will be reported separately.…”

“…Furthermore, if an imidazolyl group The preparation of poly glucose sulfates was reported in the third paper of this series.1 These highly branched polyanions were useful models to study macromolecular interactions with basic or amphoteric proteins.2 For example, polyglucose sulfate preparations of different molecular weight and different degree of substitution had different enzyme inhibitory potency. 3 Derivatives having known amounts of weaker dissociating anionic groups, such as carboxyl groups, but retaining the high molecular weight and the unique highly-branched structure of the polyglucose4 have been sought for further studies. These carboxyl derivatives have the advantage in certain biological applications of being less toxic than the sulfates, which are strong anticoagulants, b6 This paper reports the preparation of a series of non-dialyzable polyglucose carboxyl derivatives which have different carboxyl content.…”