Structure of cytochalasins and cytochalasin B binding sites in human erythrocyte membranes

Publisher Website
Google Scholar
Abstract
Twenty cytochalasins were tested for binding to and for inhibition of glucose transport in human erythrocyte membrane. In this membrane 3 cytochalasin B (CB) binding sites were identified. All but 3 cytochalasins bind at site II. Only 9 of them, which are structurally closely related, bind at site I and inhibit glucose transport. For site I (and site III) binding and glucose transport inhibitory activities the macrocyclic ring in the cytochalasin molecule must be at least 13-membered, the nature of the aromatic ring at C-10 is not important, the C-20-C-23 region makes a major contribution and the C-5-C-7 segment has relatively minor influence. These findings do not support a proposed mechanism which involves 24, C-23, C-20 and C-1 oxygen atoms for interaction of CB with glucose carrier. The structural requirements for site II activity are less stringent. The size and structure of the macrocyclic ring and the nature of aromatic residue at C-10 modulate this activity slightly, if at all. Modifications in the C-5-C-7 region of the molecule result in substantial changes in this activity.