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Synthesis of distal and proximal fleximer base analogues and evaluation in the nucleocapsid protein of HIV-1.

ABSTRACT: Anti-HIV-1 drug design has been notably challenging due to the virus' ability to mutate and develop immunity against commercially available drugs. The aims of this project were to develop a series of fleximer base analogues that not only possess inherent flexibility that can remain active when faced with binding site mutations, but also target a non-canonical, highly conserved target: the nucleocapsid protein of HIV (NC). The compounds were predicted by computational studies not to function via zinc ejection, which would endow them with significant advantages over non-specific and thus toxic zinc-ejectors. The target fleximer bases were synthesized using palladium-catalyzed cross-coupling techniques and subsequently tested against NC and HIV-1. The results of those studies are described herein.

SUBMITTER: Ku T

PROVIDER: S-EPMC6556414 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Synthesis of distal and proximal fleximer base analogues and evaluation in the nucleocapsid protein of HIV-1.

Ku Therese T Lopresti Natalie N Shirley Matthew M Mori Mattia M Marchant Jan J Heng Xiao X Botta Maurizio M Summers Michael F MF Seley-Radtke Katherine L KL

Bioorganic & medicinal chemistry 20190515 13

Anti-HIV-1 drug design has been notably challenging due to the virus' ability to mutate and develop immunity against commercially available drugs. The aims of this project were to develop a series of fleximer base analogues that not only possess inherent flexibility that can remain active when faced with binding site mutations, but also target a non-canonical, highly conserved target: the nucleocapsid protein of HIV (NC). The compounds were predicted by computational studies not to function via ...[more]

PMID: 31126822

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