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

Organic & Biomolecular Chemistry
Boris AillardSally Bloodworth

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 (1)H 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 (1)H-(15)N HSQC NMR titration experiments.

References

Jan 20, 1993·Journal of Molecular Biology·A A Adzhubei, M J Sternberg
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·D J WitterA L Castelhano
Mar 26, 1999·Protein Science : a Publication of the Protein Society·B J Stapley, T P Creamer
Jul 13, 2000·Accounts of Chemical Research·M J Burk
Jun 30, 2001·The Journal of Organic Chemistry·A MamaiJ S Madalengoitia
Jul 18, 2001·Journal of the American Chemical Society·L E BretscherR T Raines
Jul 18, 2001·Journal of the American Chemical Society·C W WuA E Barron
Jul 18, 2002·Journal of the American Chemical Society·Peter Tremmel, Armin Geyer
Aug 16, 2002·Chemistry : a European Journal·Fernando BernardiClaudio Toniolo
Nov 7, 2002·Advances in Protein Chemistry·Trevor P Creamer, Margaret N Campbell
May 23, 2003·Protein Science : a Publication of the Protein Society·Matthew P Hinderaker, Ronald T Raines
May 27, 2003·Biopolymers·Sik Lok Lam, Victor L Hsu
Sep 28, 2004·Journal of Chemical Information and Computer Sciences·Armando Navarro-VázquezErnesto Díez
Jul 16, 2005·The Journal of Organic Chemistry·Ravindranadh V Somu, Rodney L Johnson
Sep 6, 2005·The Journal of Peptide Research : Official Journal of the American Peptide Society·R ZhangJ S Madalengoitia
Aug 12, 2006·Physical Chemistry Chemical Physics : PCCP·Yihan ShaoMartin Head-Gordon
Nov 1, 2006·Protein and Peptide Letters·Rita BerisioLuigi Vitagliano
Mar 26, 2010·Journal of the American Chemical Society·Neil W OwensFrank Schweizer
Aug 8, 2012·Acta Crystallographica. Section D, Biological Crystallography·Jose Manuel Martin-GarciaAna Camara-Artigas
Feb 13, 2013·Beilstein Journal of Organic Chemistry·Swapna BhagwanthRodney L Johnson
Mar 20, 2013·Journal of Molecular Biology·Alexei A AdzhubeiAlexander A Makarov
Jun 14, 2013·Organic & Biomolecular Chemistry·Guilhem ChaubetJean Martinez
Jun 6, 2014·Organic & Biomolecular Chemistry·Arkady Khashper, William D Lubell
Sep 13, 2014·Chemistry : a European Journal·Charlotte MartinFlorine Cavelier
Nov 9, 2014·Database : the Journal of Biological Databases and Curation·Romain ChebrekJean-Christophe Gelly

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Journal of the American Chemical Society
M A Young, E S Pysh
Proceedings of the National Academy of Sciences of the United States of America
P R Schimmel, P J Flory
Acta Crystallographica. Section B, Structural Science
S Arnott, S D Dover
© 2021 Meta ULC. All rights reserved