Formation of unimolecular G-quartet from N9-modified guanine derivatives
Authors:Foster Alexis, Andrew Andrew, Bryant Hammershaimb, Spencer Robertson
Mentor:Jeremy McCallum, Associate Professor of Chemistry, Loyola Marymount University
With the recent interest in the anticancer potential of G-quadruplexes, the need exists for understanding the self-assembly of G-quadruplexes and G-quartets. Several N9-modified guanine derivatives were synthesized to examine their self-assembling properties. N9-(3,5-di-tert-butylbenzyl)-guanine, N9-(3,5-bis(tert-butyldimethylsilyloxy) benzyl)-guanine, N9-(3,5-bis(pent-4-enyloxy)benzyl)-guanine, N9-(3,5-bis(hex-5-enyloxy)benzyl)-guanine, N9-(3,5-bis(hept-6-enyloxy)benzyl)-guanine, and N9-(3,5-bis(oct-7-enyloxy)benzyl)-guanine were synthesized in good yields via coupling reactions involving 2-N-acetylguanine and benzyl bromide derivatives followed by amide deprotection. The self-assembling properties of these derivatives to form G-quartets were studied through the addition of various metals and determined by NMR and molecular modeling studies. G-quartet macrocycle formation from cation-templated ring-closing methathesis is currently under investigation.