Compounds having anti-adhesive effects on cancer cells

摘要

Compounds of the form O-(x-L)n, where O is an oligonucleoside having at least a plurality of N3′→P5′ thiophosphoramidate (NPS) internucleoside linkages, a conjugated lipid moiety L, and at least one G-rich sequence motif as described, are effective to morphologically alter and reduce adhesion of cancer cells.

主权项

1. A compound having a structure represented by o-(x-L)n, where
(a) o is a polynucleoside moiety comprising a sequence of nucleosides and linkage moieties, wherein (i) at least 50% of said linkage moieties are selected from: 3′-NH—P(O)(S−)-5′; 3′-NH—P(O)(S−)—{OR}m—Y—P(O)(S−)-5′; and 3′-Y—R—O—P(O)(S−)-5′; and at least 75% of internucleoside linkage moieties are selected from 3′-NH—P(O)(S−)-5′ and 3′-NH—P(O)(S−)—{OR}m—Y—P(O)(S−)-5′; where Y is NH or O; R is a stable linear chain two to six atoms in length having bonds selected from alkyl, alkenyl, ether, thioether, and amino; and m is 1 to 3; and (ii) said polynucleoside moiety includes at least one motif selected from GGG, GGWGG, and GGWWGG, containing residues selected from G and W, where G is guanosine and W is a nucleoside or the moiety —OR—, where R is as defined above, and the inter-residue linkages within said motif are N3′→P5′ thiophosphoramidate (3′-NH—P(O)(S−)-5′) or phosphorothioate (3′-O—P(O)(S−)-5′) linkages; (b) x is an optional linker group, (c) L is a lipid moiety comprising a linear hydrocarbon moiety at least 12 carbon atoms in length, and (d) n is 1 or 2; wherein the compound o-(x-L)n is not a telomerase inhibitor.