Bromotryptophans and their incorporation in cyclic and bicyclic privileged peptides

Júlia García-Pindado; Tom Willemse; Rebecca Goss; Bert U. W. Maes; Ernest Giralt; Steven Ballet; Meritxell Teixidó

doi:10.1002/bip.23112

Bromotryptophans and their incorporation in cyclic and bicyclic privileged peptides

Júlia García-Pindado, Tom Willemse, Rebecca Goss, Bert U. W. Maes, Ernest Giralt, Steven Ballet, Meritxell Teixidó

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

Abstract

While revisiting biologically active natural peptides, the importance of the tryptophan residue became clear. In this article, the incorporation of this amino acid, brominated at different positions of the indole ring, into cyclic peptides was successfully achieved. These products demonstrated improved properties in terms of passive diffusion, permeability across membranes, biostability in human serum and cytotoxicity. Moreover, these brominated tryptophans at positions 5, 6, or 7 proved to be compatible as building blocks to prepare bicyclic stapled peptides by performing on-resin Suzuki-Miyaura cross-coupling reactions.

Original language	English
Journal	Biopolymers
Volume	Early View
Early online date	12 Mar 2018
DOIs	https://doi.org/10.1002/bip.23112
Publication status	E-pub ahead of print - 12 Mar 2018

Keywords

Biostability
Bromination
On-resin Miyaura and Suzuki-Miyaura cross-coupling
PAMPA
Solid-phase peptide synthesis
Tryptophan

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10.1002/bip.23112

Garcia-Pindado-2018-Bromotryptophans-Biopolymers-AAM
© 2018, Wiley Periodicals, Inc. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/bip.23112
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title = "Bromotryptophans and their incorporation in cyclic and bicyclic privileged peptides",

abstract = "While revisiting biologically active natural peptides, the importance of the tryptophan residue became clear. In this article, the incorporation of this amino acid, brominated at different positions of the indole ring, into cyclic peptides was successfully achieved. These products demonstrated improved properties in terms of passive diffusion, permeability across membranes, biostability in human serum and cytotoxicity. Moreover, these brominated tryptophans at positions 5, 6, or 7 proved to be compatible as building blocks to prepare bicyclic stapled peptides by performing on-resin Suzuki-Miyaura cross-coupling reactions.",

keywords = "Biostability, Bromination, On-resin Miyaura and Suzuki-Miyaura cross-coupling, PAMPA, Solid-phase peptide synthesis, Tryptophan",

author = "J{\'u}lia Garc{\'i}a-Pindado and Tom Willemse and Rebecca Goss and Maes, {Bert U. W.} and Ernest Giralt and Steven Ballet and Meritxell Teixid{\'o}",

note = "This work was supported by MINECO-FEDER (BIO2016–75327-R) and the Generalitat de Catalunya (XRB and 2014-SGR-521). J{\'u}lia Garc{\'i}a was supported by an FPU grant (AP2012–6464). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO. The IWT Flanders and Janssen Pharmaceutica are thanked for providing financial support of T.W. B.U.W.M ad S.B. thank the Research Foundation Flanders (FWO Vlaanderen; Scientific Research Network (WOG)).",

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month = mar,

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language = "English",

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T1 - Bromotryptophans and their incorporation in cyclic and bicyclic privileged peptides

AU - García-Pindado, Júlia

AU - Willemse, Tom

AU - Goss, Rebecca

AU - Maes, Bert U. W.

AU - Giralt, Ernest

AU - Ballet, Steven

AU - Teixidó, Meritxell

N1 - This work was supported by MINECO-FEDER (BIO2016–75327-R) and the Generalitat de Catalunya (XRB and 2014-SGR-521). Júlia García was supported by an FPU grant (AP2012–6464). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO. The IWT Flanders and Janssen Pharmaceutica are thanked for providing financial support of T.W. B.U.W.M ad S.B. thank the Research Foundation Flanders (FWO Vlaanderen; Scientific Research Network (WOG)).

PY - 2018/3/12

Y1 - 2018/3/12

N2 - While revisiting biologically active natural peptides, the importance of the tryptophan residue became clear. In this article, the incorporation of this amino acid, brominated at different positions of the indole ring, into cyclic peptides was successfully achieved. These products demonstrated improved properties in terms of passive diffusion, permeability across membranes, biostability in human serum and cytotoxicity. Moreover, these brominated tryptophans at positions 5, 6, or 7 proved to be compatible as building blocks to prepare bicyclic stapled peptides by performing on-resin Suzuki-Miyaura cross-coupling reactions.

AB - While revisiting biologically active natural peptides, the importance of the tryptophan residue became clear. In this article, the incorporation of this amino acid, brominated at different positions of the indole ring, into cyclic peptides was successfully achieved. These products demonstrated improved properties in terms of passive diffusion, permeability across membranes, biostability in human serum and cytotoxicity. Moreover, these brominated tryptophans at positions 5, 6, or 7 proved to be compatible as building blocks to prepare bicyclic stapled peptides by performing on-resin Suzuki-Miyaura cross-coupling reactions.

KW - Biostability

KW - Bromination

KW - On-resin Miyaura and Suzuki-Miyaura cross-coupling

KW - PAMPA

KW - Solid-phase peptide synthesis

KW - Tryptophan

U2 - 10.1002/bip.23112

DO - 10.1002/bip.23112

M3 - Article

SN - 1097-0282

VL - Early View

JO - Biopolymers

JF - Biopolymers

ER -

Bromotryptophans and their incorporation in cyclic and bicyclic privileged peptides

Abstract

Keywords

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