Abstract
Evolution of Clickable Aptamers in Pursuit of a 2G12 Mimotope\r The lack of an HIV vaccine lies in part due to effective immune evasion and instability of the envelop glycoprotein (Env). In pursuit of simplified analogs, glycosylated aptamers were evolved by the SELMA procedure, using libraries with a low occurrence of alkyne–containing sites in the random region to reduce the number glycosylation sites in the mature aptamer. Two different libraries rapidly converged to a recurring sequence motif. Mfold studies suggested a structure for the recurring sequence, which was in agreement with truncations studies. A SELMA selection designed to dimerize this motif around an optimal spacer instead resulted in deletion of the second copy. The motif selected at 25oC was found to be unstable at 37oC.\r Progress Toward (-)-spongidepsin and Analogs\r Homocrotylation reagents previously described by this group were employed for the rapid synthesis of C1–5 and C6–13 fragments of (-)-spongidepsin. Cobalt protection of the terminal acetylene was employed as an alternative to the standard late–stage installation of the acetylene. Steglich esterification and peptide coupling constructed the linear framework of\r v\r spongidepsin, with subsequent acetylene protection and ring–closing methathesis smoothly affording the macrocycle. Reduction of the internal double bond without affecting the protected acetylene remains challenging. The use of in situ generated diimide is prone to side reactions and decomposition. To a lesser extent, hydroboration/protodeboronation schemes have also been problematic.