Iminoboronates are efficient intermediates for selective, rapid and reversible N -terminal cysteine functionalisation

Chemical Science
Hélio FaustinoPedro M P Gois

Abstract

We show that formyl benzeno boronic acids (2FBBA) selectively react with N-terminal cysteines to yield a boronated thiazolidine featuring a B-N bond. The reaction exhibits a very rapid constant rate (2.38 ± 0.23 × 102 M-1 s-1) under mild aqueous conditions (pH 7.4, 23 °C) and tolerates different amino acids at the position adjacent to the N-cysteine. DFT calculations highlighted the diastereoselective nature of this ligation reaction and support the involvement of the proximal boronic acid in the activation of the imine functionality and the stabilisation of the boronated thiazolidine through a chelate effect. The 2FBBA reagent allowed the effective functionalisation of model peptides (C-ovalbumin and a laminin fragment) and the boronated thiazolidine construct was shown to be stable over time, though the reaction was reversible in the presence of benzyl hydroxylamine. The reaction proved to be highly chemoselective, and 2FBBA was used to functionalize the N-terminal cysteine of calcitonin in the presence of a potentially competing in-chain thiol group. This exquisite selectivity profile enabled the dual functionalisation of calcitonin and the interactive orthogonal modification of this peptide when 2FBBA was combined with conv...Continue Reading

References

Nov 4, 1994·Science·P E DawsonS B Kent
Aug 24, 2006·Nature Reviews. Molecular Cell Biology·Jianming Xie, Peter G Schultz
Feb 25, 2009·Chemistry, an Asian Journal·Justin M ChalkerBenjamin G Davis
Aug 6, 2011·Accounts of Chemical Research·John T Ngo, David A Tirrell
Nov 17, 2011·Nature Chemical Biology·Nicholas Stephanopoulos, Matthew B Francis
Mar 8, 2012·Journal of the American Chemical Society·Giulio CasiDario Neri
May 31, 2012·Journal of the American Chemical Society·Pedro M S D CalPedro M P Gois
Oct 5, 2013·Nature Protocols·Gonçalo J L BernardesGiulio Casi
Oct 19, 2013·Journal of the American Chemical Society·Mohammad RashidianMark D Distefano
Nov 22, 2013·Chemical Communications : Chem Comm·Pedro M S D CalPedro M P Gois
Dec 18, 2013·Organic & Biomolecular Chemistry·Yue Yuan, Gaolin Liang
Jan 15, 2014·Bioconjugate Chemistry·Oleksandr KonievAlain Wagner
Jan 21, 2014·ACS Chemical Biology·David M PattersonJennifer A Prescher
Apr 2, 2014·Chemical Communications : Chem Comm·Paul MoodyStephen Caddick
May 27, 2014·Journal of the American Chemical Society·Amit SachdevaJason W Chin
Jul 22, 2014·Chembiochem : a European Journal of Chemical Biology·Jan GrünewaldBernhard H Geierstanger
Jul 30, 2014·Angewandte Chemie·Pedro M S D CalPedro M P Gois
Dec 3, 2014·Current Opinion in Chemical Biology·D Alexander Shannon, Eranthie Weerapana
Feb 24, 2015·Chemical Reviews·Omar Boutureira, Gonçalo J L Bernardes
Apr 1, 2015·Nature Communications·Antoine MaruaniStephen Caddick
Apr 23, 2015·Chemistry : a European Journal·Pedro M S D CalPedro M P Gois
Jul 1, 2015·Beilstein Journal of Organic Chemistry·Michaela MühlbergChristian P R Hackenberger
Aug 28, 2015·Chemistry : a European Journal·Anupam Bandyopadhyay, Jianmin Gao
Jan 23, 2016·Nature Chemistry·Yichao Huang, Lei Liu
Jan 23, 2016·Nature Chemistry·Nikolaus KrallGonçalo J L Bernardes
Jan 23, 2016·Nature Chemistry·Chi ZhangBradley L Pentelute
Jan 23, 2016·Chemical Society Reviews·Qi-Ying HuRoberto Adamo
Jun 1, 2015·Chemical Science·Pascal SchmidtDennis Gillingham

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Citations

Oct 23, 2018·Chemical Communications : Chem Comm·Daniel Bermejo-VelascoOommen P Varghese
Oct 16, 2018·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Seiji Sakamoto, Itaru Hamachi
Jun 21, 2017·Nature Chemical Biology·Christian B Rosen, Matthew B Francis
May 31, 2019·Organic & Biomolecular Chemistry·Kaicheng LiJianmin Gao
Jun 4, 2019·Chemical Society Reviews·João P M AntónioPedro M P Gois
Sep 3, 2020·Chemical Science·T M Simon TangLouis Y P Luk
May 4, 2018·Angewandte Chemie·Burcin Akgun, Dennis G Hall
Jun 12, 2018·Chemistry : a European Journal·Ricardo M R M LopesPedro M P Gois
Jun 17, 2020·Organic & Biomolecular Chemistry·Neelesh C ReddyVishal Rai
Feb 1, 2020·Materials Chemistry Frontiers·Yan ZhangOlof Ramström
Jun 8, 2021·Chemical Science·Landa PurushottamVishal Rai
Jun 29, 2021·Chemical Communications : Chem Comm·Mohan KumarVishal Rai
Jun 25, 2021·Chemical Science·Saurav ChatterjeeAnupam Bandyopadhyay
Jan 1, 2020·Nature Reviews. Chemistry·Sean S Nguyen, Jennifer A Prescher
Aug 16, 2018·Accounts of Chemical Research·Samantha Cambray, Jianmin Gao
Sep 12, 2017·Journal of the American Chemical Society·Burcin AkgunDennis G Hall
May 4, 2018·Biomacromolecules·Yanjing Wang, Chi Wu
Sep 15, 2021·Chembiochem : a European Journal of Chemical Biology·Karl D BruneKaspars Tārs
Nov 18, 2021·Journal of the American Chemical Society·Katsuya MaruyamaMotomu Kanai

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Methods Mentioned

BETA
X-ray
acetylation

Software Mentioned

DFT

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