Syed Tasadaque Ali Shah

Title : Synthesis of monoacylglycerols (MAGs) lipids for the use in In meso crystallisation of membrane proteins

Abstract:

The crystallisation of membrane proteins in lipidic mesophases by the so-called in meso method using cis-monounsaturated monoacylglycerols (MAGs) has afforded diffraction quality crystals and high-resolution structures of tens of unique membrane proteins. One most important example of crystallization is “Beta-2 adrenergic receptor-Gs protein complex” published in Nature in 2011, this publication played a crucial role in the 2012 Nobel Prize in Chemistry. To date, the benchmark lipids behind this success have been monoacylglycerols, with monoolein being the most widely used. With a view to rationally designing novel mesophase systems the challenge remains to deconvolute the relationship between lipid molecular structure, sample composition, and phase microstructure. Here we present our approach via a modular synthesis of a homologous series of MAGs. The devised modular methodology allows for the tailoring of the acyl chain length and olefin position/geometry. The synthesis revolves around the Suzuki-Miyaura coupling strategy of a cis-1-iodo-1-alkene with the desired ester derived from the terminally unsaturated carboxylic acid. Phase behaviour and microstructure are determined through small angle X-ray scattering measurements (SAXS). Finally, the ability of these novel lipids to support in meso crystallisation of novel integral membrane proteins has been evaluated. 

Audience Take Away: 

•    Design and synthesis of Monoacylglycerols (MAGs) lipids will be discussed
•    Purifications methods of Monoacylglycerols (MAGs) will be discussed
•    Library of Monoacylglycerols will be discussed

Biography:

Dr Tasadaque is an Associate Professor at Sukkur IBA University, achieved DAAD Scholarship in year 2000, he achieved PhD in 2003 from the University of Tuebingen Germany with “Magna Cum Laude”.

Tasadaque worked around 10 years at University College Dublin and Trinity College Dublin and is author and co-author of more than 50 peer-reviewed publications such as Nature and Science. He developed an efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible SARS corona virus main.

He is a co-author in Nature in 2011 with Nobel Laureate Prof Brian Kobilka, this publication played a crucial role in the 2012 Nobel Prize in Chemistry. Contribution of Tasadaque is recognized in his Nobel Prize award lecture.

https://www.nobelprize.org/prizes/chemistry/2012/kobilka/lecture/.