Synthesis and evaluation of peptidic thrombin inhibitors bearing acid-stable sulfotyrosine analogues

L.J. Dowman; Stijn Agten; J. Ripoll-Rozada; Bárbara Calisto; P.J.B. Pereira; R.J. Payne

doi:10.1039/d1cc04742f

Synthesis and evaluation of peptidic thrombin inhibitors bearing acid-stable sulfotyrosine analogues

L.J. Dowman
, Stijn Agten
, J. Ripoll-Rozada
, Bárbara Calisto
, P.J.B. Pereira
, R.J. Payne^*

^*Corresponding author for this work

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

Abstract

Tyrosine sulfation is an important post-translational modification of peptides and proteins which underpins and modulates many protein-protein interactions. In order to overcome the inherent instability of the native modification, we report the synthesis of two sulfonate analogues and their incorporation into two thrombin-inhibiting sulfopeptides. The effective mimicry of these sulfonate analogues for native sulfotyrosine was validated in the context of their thrombin inhibitory activity and binding mode, as determined by X-ray crystallography.

Original language	English
Pages (from-to)	10923-10926
Number of pages	4
Journal	Chemical Communications
Volume	57
Issue number	83
DOIs	https://doi.org/10.1039/d1cc04742f
Publication status	Published - 19 Oct 2021
Externally published	Yes

Keywords

TYROSINE SULFATION
ANTICOAGULANT
SULFOPEPTIDES
SULFOPROTEINS
RECOGNITION
REVEALS
BINDING
SALIVA

Access to Document

10.1039/d1cc04742f

Cite this

@article{927af72b04944d27b3c8d2d50270ad24,

title = "Synthesis and evaluation of peptidic thrombin inhibitors bearing acid-stable sulfotyrosine analogues",

abstract = "Tyrosine sulfation is an important post-translational modification of peptides and proteins which underpins and modulates many protein-protein interactions. In order to overcome the inherent instability of the native modification, we report the synthesis of two sulfonate analogues and their incorporation into two thrombin-inhibiting sulfopeptides. The effective mimicry of these sulfonate analogues for native sulfotyrosine was validated in the context of their thrombin inhibitory activity and binding mode, as determined by X-ray crystallography.",

keywords = "TYROSINE SULFATION, ANTICOAGULANT, SULFOPEPTIDES, SULFOPROTEINS, RECOGNITION, REVEALS, BINDING, SALIVA",

author = "L.J. Dowman and Stijn Agten and J. Ripoll-Rozada and B{\'a}rbara Calisto and P.J.B. Pereira and R.J. Payne",

note = "Funding Information: We would like to acknowledge the National Health and Medical Research Council (APP1174941 to R. J. P) and Contract DL 57/2016/CP1355/CT0011 from Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia, Portugal (to J. R.-R.) for funding. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2021.",

year = "2021",

month = oct,

day = "19",

doi = "10.1039/d1cc04742f",

language = "English",

volume = "57",

pages = "10923--10926",

journal = "Chemical Communications",

issn = "1359-7345",

publisher = "Royal Society of Chemistry",

number = "83",

}

TY - JOUR

T1 - Synthesis and evaluation of peptidic thrombin inhibitors bearing acid-stable sulfotyrosine analogues

AU - Dowman, L.J.

AU - Agten, Stijn

AU - Ripoll-Rozada, J.

AU - Calisto, Bárbara

AU - Pereira, P.J.B.

AU - Payne, R.J.

N1 - Funding Information: We would like to acknowledge the National Health and Medical Research Council (APP1174941 to R. J. P) and Contract DL 57/2016/CP1355/CT0011 from Fundação para a Ciência e a Tecnologia, Portugal (to J. R.-R.) for funding. Publisher Copyright: © The Royal Society of Chemistry 2021.

PY - 2021/10/19

Y1 - 2021/10/19

N2 - Tyrosine sulfation is an important post-translational modification of peptides and proteins which underpins and modulates many protein-protein interactions. In order to overcome the inherent instability of the native modification, we report the synthesis of two sulfonate analogues and their incorporation into two thrombin-inhibiting sulfopeptides. The effective mimicry of these sulfonate analogues for native sulfotyrosine was validated in the context of their thrombin inhibitory activity and binding mode, as determined by X-ray crystallography.

AB - Tyrosine sulfation is an important post-translational modification of peptides and proteins which underpins and modulates many protein-protein interactions. In order to overcome the inherent instability of the native modification, we report the synthesis of two sulfonate analogues and their incorporation into two thrombin-inhibiting sulfopeptides. The effective mimicry of these sulfonate analogues for native sulfotyrosine was validated in the context of their thrombin inhibitory activity and binding mode, as determined by X-ray crystallography.

KW - TYROSINE SULFATION

KW - ANTICOAGULANT

KW - SULFOPEPTIDES

KW - SULFOPROTEINS

KW - RECOGNITION

KW - REVEALS

KW - BINDING

KW - SALIVA

U2 - 10.1039/d1cc04742f

DO - 10.1039/d1cc04742f

M3 - Article

C2 - 34596182

SN - 1359-7345

VL - 57

SP - 10923

EP - 10926

JO - Chemical Communications

JF - Chemical Communications

IS - 83

ER -

Synthesis and evaluation of peptidic thrombin inhibitors bearing acid-stable sulfotyrosine analogues

Abstract

Keywords

Access to Document

Fingerprint

Cite this