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Synthesis and evaluation of a (3R, 6S, 9S)-2-oxo-1-azabicyclo[4.3.0]nonane scaffold as a mimic of Xaa-transPro in poly-L-proline type II helix conformation

Synthesis and evaluation of a (3R, 6S, 9S)-2-oxo-1-azabicyclo[4.3.0]nonane scaffold as a mimic of Xaa-transPro in poly-L-proline type II helix conformation
Synthesis and evaluation of a (3R, 6S, 9S)-2-oxo-1-azabicyclo[4.3.0]nonane scaffold as a mimic of Xaa-transPro in poly-L-proline type II helix conformation
We describe the development of a small-molecule mimic of Xaa-trans-Pro dipeptide in poly-L-proline type II helix conformation, based upon a (3R,6S,9S)-2-oxo-1-azabicyclo[4.3.0]nonane core structure. Stereoselective synthesis of the mimic from L-pyroglutamic acid is achieved in twelve linear steps and 9.9% yield. Configurational and conformational analyses are conducted using a combination of 1H NMR spectroscopy, X-ray crystallography and circular dichroism spectroscopy; and evaluation of the mimic as a promising surrogate dipeptide, in a protein–protein interaction between the SH3 domain of human Fyn kinase (Fyn SH3) and peptidomimetics of its biological ligand, are conducted by 1H-15N HSQC NMR titration experiments.
1477-0520
4562-4569
Aillard, Boris
18da6bd3-4081-40b8-89a7-4aae3f0bc767
Kilburn, Jeremy D.
e64ded70-825a-40ec-816b-c4605e007e7a
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Tizzard, Graham J.
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Findlow, I.Stuart C.
27cf014b-9d9f-4a59-9791-c704a04c6b52
Werner, Jörn M.
1b02513a-8310-4f4f-adac-dc2a466bd115
Bloodworth, Sally
943160fc-1b70-4c29-b2e3-b7785cee8a0c
Aillard, Boris
18da6bd3-4081-40b8-89a7-4aae3f0bc767
Kilburn, Jeremy D.
e64ded70-825a-40ec-816b-c4605e007e7a
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Tizzard, Graham J.
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Findlow, I.Stuart C.
27cf014b-9d9f-4a59-9791-c704a04c6b52
Werner, Jörn M.
1b02513a-8310-4f4f-adac-dc2a466bd115
Bloodworth, Sally
943160fc-1b70-4c29-b2e3-b7785cee8a0c

Aillard, Boris, Kilburn, Jeremy D., Blaydes, Jeremy P., Tizzard, Graham J., Findlow, I.Stuart C., Werner, Jörn M. and Bloodworth, Sally (2015) Synthesis and evaluation of a (3R, 6S, 9S)-2-oxo-1-azabicyclo[4.3.0]nonane scaffold as a mimic of Xaa-transPro in poly-L-proline type II helix conformation. Organic & Biomolecular Chemistry, 13, 4562-4569. (doi:10.1039/c5ob00180c).

Record type: Article

Abstract

We describe the development of a small-molecule mimic of Xaa-trans-Pro dipeptide in poly-L-proline type II helix conformation, based upon a (3R,6S,9S)-2-oxo-1-azabicyclo[4.3.0]nonane core structure. Stereoselective synthesis of the mimic from L-pyroglutamic acid is achieved in twelve linear steps and 9.9% yield. Configurational and conformational analyses are conducted using a combination of 1H NMR spectroscopy, X-ray crystallography and circular dichroism spectroscopy; and evaluation of the mimic as a promising surrogate dipeptide, in a protein–protein interaction between the SH3 domain of human Fyn kinase (Fyn SH3) and peptidomimetics of its biological ligand, are conducted by 1H-15N HSQC NMR titration experiments.

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Submitted date: 29 January 2015
Accepted/In Press date: 10 March 2015
Published date: 10 March 2015
Organisations: Chemistry, Cancer Sciences, Centre for Biological Sciences

Identifiers

Local EPrints ID: 375710
URI: https://eprints.soton.ac.uk/id/eprint/375710
ISSN: 1477-0520
PURE UUID: b69e473b-b743-4633-8c20-48bd873861dd
ORCID for Jeremy P. Blaydes: ORCID iD orcid.org/0000-0001-8525-0209
ORCID for Graham J. Tizzard: ORCID iD orcid.org/0000-0002-1577-5779
ORCID for Jörn M. Werner: ORCID iD orcid.org/0000-0002-4712-1833
ORCID for Sally Bloodworth: ORCID iD orcid.org/0000-0003-2219-3635

Catalogue record

Date deposited: 02 Apr 2015 13:19
Last modified: 18 May 2019 00:36

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