Design and synthesis of unprecedented 9-and 10-membered cyclonucleosides with PRMT5 inhibitory activity

Shuhei Kawamura; Rachel L. Palte; Hai-Young Kim; Josep Sauri; Christopher Sondey; My S. Mansueto; Michael D. Altman; Michelle R. Machacek

doi:10.1016/j.bmc.2022.116820

Design and synthesis of unprecedented 9-and 10-membered cyclonucleosides with PRMT5 inhibitory activity

Shuhei Kawamura
, Rachel L. Palte
, Hai-Young Kim
, Josep Sauri
, Christopher Sondey
, My S. Mansueto
, Michael D. Altman
, Michelle R. Machacek

Producción científica: Artículo en revista indizada › Artículo › revisión exhaustiva

9 Citas (Scopus)

Resumen

Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5 ' cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5.

Idioma original	Inglés
Número de artículo	116820
Número de páginas	6
Publicación	Bioorganic and Medicinal Chemistry
Volumen	66
Fecha en línea anticipada	may 2022
DOI	https://doi.org/10.1016/j.bmc.2022.116820
Estado	Publicada - 15 jul 2022
Publicado de forma externa	Sí

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10.1016/j.bmc.2022.116820

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@article{8a3be1641a3a4d03a0b50fd5d77a14a6,

title = "Design and synthesis of unprecedented 9-and 10-membered cyclonucleosides with PRMT5 inhibitory activity",

abstract = "Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5 ' cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5.",

keywords = "Cyclonucleoside, Medicinal chemistry, Molecular modeling, Nucleoside, Prmt5, PRMT5 inhibitor, X-ray crystallography",

author = "Shuhei Kawamura and Palte, \{Rachel L.\} and Hai-Young Kim and Josep Sauri and Christopher Sondey and Mansueto, \{My S.\} and Altman, \{Michael D.\} and Machacek, \{Michelle R.\}",

year = "2022",

month = jul,

day = "15",

doi = "10.1016/j.bmc.2022.116820",

language = "English",

volume = "66",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

}

TY - JOUR

T1 - Design and synthesis of unprecedented 9-and 10-membered cyclonucleosides with PRMT5 inhibitory activity

AU - Kawamura, Shuhei

AU - Palte, Rachel L.

AU - Kim, Hai-Young

AU - Sauri, Josep

AU - Sondey, Christopher

AU - Mansueto, My S.

AU - Altman, Michael D.

AU - Machacek, Michelle R.

PY - 2022/7/15

Y1 - 2022/7/15

N2 - Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5 ' cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5.

AB - Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5 ' cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5.

KW - Cyclonucleoside

KW - Medicinal chemistry

KW - Molecular modeling

KW - Nucleoside

KW - Prmt5

KW - PRMT5 inhibitor

KW - X-ray crystallography

UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000802657100004&DestLinkType=FullRecord&DestApp=WOS_CPL

U2 - 10.1016/j.bmc.2022.116820

DO - 10.1016/j.bmc.2022.116820

M3 - Article

C2 - 35594650

SN - 0968-0896

VL - 66

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

M1 - 116820

ER -

Design and synthesis of unprecedented 9-and 10-membered cyclonucleosides with PRMT5 inhibitory activity

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