Guanidinoneomycin-Maleimide Molecular Transporter: Synthesis, Chemistry and Cellular Uptake

Kaivin Hadidi; Maria Cristina Bellucci; Sergio Dall'Angelo; Alasdair Leeson-Payne; Justin J Rochford; Jeffery D.  Esko; Yitzhak Tor; Alessandro Volonterio

doi:10.1039/D1OB01101D

Guanidinoneomycin-Maleimide Molecular Transporter: Synthesis, Chemistry and Cellular Uptake

Kaivin Hadidi, Maria Cristina Bellucci, Sergio Dall'Angelo, Alasdair Leeson-Payne, Justin J Rochford, Jeffery D. Esko, Yitzhak Tor^* (Corresponding Author), Alessandro Volonterio^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Guanidinoglycosides are a class of non-cytotoxic molecular transporters capable of delivering high molecular weight bioactive cargos into cells at low nanomolar concentrations. Efficient bioconjugation with guanidinoglycosides has been previously demonstrated by utilizing a guanidinoneomycin decorated with a reactive but also unstable N-hydroxysuccinimmide ester-containing linker. Herein we report the synthesis, chemistry, and application of a new, stable guanidinoneomycin derivative armed with a highly specific maleimide moiety which allows for thiol-maleimide click chemistry, a highly popular bioconjugation strategy, widening the field of application of these intriguing and useful delivery vehicles.

Original language	English
Pages (from-to)	6513-6520
Number of pages	8
Journal	Organic & Biomolecular Chemistry
Volume	19
Issue number	29
Early online date	6 Jul 2021
DOIs	https://doi.org/10.1039/D1OB01101D
Publication status	Published - 7 Aug 2021

Bibliographical note

We thank the Fulbright Program for a Research Scholar Fellowship (A.V.) and the National Science Foundation for support (via grant number CHE-1303554), the Biotechnology and Biological Sciences Research Council [BB/K017772/1] (J.J.R.) as well as the Chemistry and Biochemistry MS and NMR Facilities.

Data Availability Statement

Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ob01101d

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Hadidi_etal_OBC_Guanidinoneomycin_Maleimide_Molecular_AAMAccepted author manuscript, 451 KBLicence: Unspecified

Cite this

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title = "Guanidinoneomycin-Maleimide Molecular Transporter: Synthesis, Chemistry and Cellular Uptake ",

abstract = "Guanidinoglycosides are a class of non-cytotoxic molecular transporters capable of delivering high molecular weight bioactive cargos into cells at low nanomolar concentrations. Efficient bioconjugation with guanidinoglycosides has been previously demonstrated by utilizing a guanidinoneomycin decorated with a reactive but also unstable N-hydroxysuccinimmide ester-containing linker. Herein we report the synthesis, chemistry, and application of a new, stable guanidinoneomycin derivative armed with a highly specific maleimide moiety which allows for thiol-maleimide click chemistry, a highly popular bioconjugation strategy, widening the field of application of these intriguing and useful delivery vehicles.",

author = "Kaivin Hadidi and Bellucci, {Maria Cristina} and Sergio Dall'Angelo and Alasdair Leeson-Payne and Rochford, {Justin J} and Esko, {Jeffery D.} and Yitzhak Tor and Alessandro Volonterio",

note = "We thank the Fulbright Program for a Research Scholar Fellowship (A.V.) and the National Science Foundation for support (via grant number CHE-1303554), the Biotechnology and Biological Sciences Research Council [BB/K017772/1] (J.J.R.) as well as the Chemistry and Biochemistry MS and NMR Facilities. ",

year = "2021",

month = aug,

day = "7",

doi = "10.1039/D1OB01101D",

language = "English",

volume = "19",

pages = "6513--6520",

journal = "Organic & Biomolecular Chemistry",

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publisher = "The Royal Society of Chemistry",

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TY - JOUR

T1 - Guanidinoneomycin-Maleimide Molecular Transporter

T2 - Synthesis, Chemistry and Cellular Uptake

AU - Hadidi, Kaivin

AU - Bellucci, Maria Cristina

AU - Dall'Angelo, Sergio

AU - Leeson-Payne, Alasdair

AU - Rochford, Justin J

AU - Esko, Jeffery D.

AU - Tor, Yitzhak

AU - Volonterio, Alessandro

N1 - We thank the Fulbright Program for a Research Scholar Fellowship (A.V.) and the National Science Foundation for support (via grant number CHE-1303554), the Biotechnology and Biological Sciences Research Council [BB/K017772/1] (J.J.R.) as well as the Chemistry and Biochemistry MS and NMR Facilities.

PY - 2021/8/7

Y1 - 2021/8/7

N2 - Guanidinoglycosides are a class of non-cytotoxic molecular transporters capable of delivering high molecular weight bioactive cargos into cells at low nanomolar concentrations. Efficient bioconjugation with guanidinoglycosides has been previously demonstrated by utilizing a guanidinoneomycin decorated with a reactive but also unstable N-hydroxysuccinimmide ester-containing linker. Herein we report the synthesis, chemistry, and application of a new, stable guanidinoneomycin derivative armed with a highly specific maleimide moiety which allows for thiol-maleimide click chemistry, a highly popular bioconjugation strategy, widening the field of application of these intriguing and useful delivery vehicles.

AB - Guanidinoglycosides are a class of non-cytotoxic molecular transporters capable of delivering high molecular weight bioactive cargos into cells at low nanomolar concentrations. Efficient bioconjugation with guanidinoglycosides has been previously demonstrated by utilizing a guanidinoneomycin decorated with a reactive but also unstable N-hydroxysuccinimmide ester-containing linker. Herein we report the synthesis, chemistry, and application of a new, stable guanidinoneomycin derivative armed with a highly specific maleimide moiety which allows for thiol-maleimide click chemistry, a highly popular bioconjugation strategy, widening the field of application of these intriguing and useful delivery vehicles.

U2 - 10.1039/D1OB01101D

DO - 10.1039/D1OB01101D

M3 - Article

SN - 1477-0520

VL - 19

SP - 6513

EP - 6520

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 29

ER -

Guanidinoneomycin-Maleimide Molecular Transporter: Synthesis, Chemistry and Cellular Uptake

Abstract

Bibliographical note

Data Availability Statement

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