Design and synthesis of a series of truncated neplanocin fleximers

Sarah C.  Zimmermann; Elizaveta  O’Neill; Godwin Ebiloma; Lynsey J. M.  Wallace; Harry P. De Koning; Katherine L.  Seley-Radtke

doi:10.3390/molecules191221200

Design and synthesis of a series of truncated neplanocin fleximers

Sarah C. Zimmermann, Elizaveta O’Neill, Godwin Ebiloma, Lynsey J. M. Wallace, Harry P. De Koning, Katherine L. Seley-Radtke

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Abstract

In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular study was to synthesize the truncated neplanocin A fleximers to investigate their potential anti-protozoan activities by inhibition of S-adenosylhomocysteine hydrolase (SAHase). The three fleximers tested displayed poor anti-trypanocidal activities, with EC50 values around 200 μM. Further studies of the corresponding ribose fleximers, most closely related to the natural nucleoside substrates, revealed low affinity for the known T. brucei nucleoside transporters P1 and P2, which may be the reason for the lack of trypanocidal activity observed

Original language	English
Pages (from-to)	21200-21214
Journal	Molecules
Volume	19
DOIs	https://doi.org/10.3390/molecules191221200
Publication status	Published - 16 Dec 2014

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title = "Design and synthesis of a series of truncated neplanocin fleximers",

abstract = "In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular study was to synthesize the truncated neplanocin A fleximers to investigate their potential anti-protozoan activities by inhibition of S-adenosylhomocysteine hydrolase (SAHase). The three fleximers tested displayed poor anti-trypanocidal activities, with EC50 values around 200 μM. Further studies of the corresponding ribose fleximers, most closely related to the natural nucleoside substrates, revealed low affinity for the known T. brucei nucleoside transporters P1 and P2, which may be the reason for the lack of trypanocidal activity observed",

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T1 - Design and synthesis of a series of truncated neplanocin fleximers

AU - Zimmermann, Sarah C.

AU - O’Neill, Elizaveta

AU - Ebiloma, Godwin

AU - Wallace, Lynsey J. M.

AU - De Koning, Harry P.

AU - Seley-Radtke, Katherine L.

PY - 2014/12/16

Y1 - 2014/12/16

N2 - In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular study was to synthesize the truncated neplanocin A fleximers to investigate their potential anti-protozoan activities by inhibition of S-adenosylhomocysteine hydrolase (SAHase). The three fleximers tested displayed poor anti-trypanocidal activities, with EC50 values around 200 μM. Further studies of the corresponding ribose fleximers, most closely related to the natural nucleoside substrates, revealed low affinity for the known T. brucei nucleoside transporters P1 and P2, which may be the reason for the lack of trypanocidal activity observed

AB - In an effort to study the effects of flexibility on enzyme recognition and activity, we have developed several different series of flexible nucleoside analogues in which the purine base is split into its respective imidazole and pyrimidine components. The focus of this particular study was to synthesize the truncated neplanocin A fleximers to investigate their potential anti-protozoan activities by inhibition of S-adenosylhomocysteine hydrolase (SAHase). The three fleximers tested displayed poor anti-trypanocidal activities, with EC50 values around 200 μM. Further studies of the corresponding ribose fleximers, most closely related to the natural nucleoside substrates, revealed low affinity for the known T. brucei nucleoside transporters P1 and P2, which may be the reason for the lack of trypanocidal activity observed

U2 - 10.3390/molecules191221200

DO - 10.3390/molecules191221200

M3 - Article

SN - 1420-3049

VL - 19

SP - 21200

EP - 21214

JO - Molecules

JF - Molecules

ER -

Design and synthesis of a series of truncated neplanocin fleximers

Abstract

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