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Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Synthetic Approaches to Functionalized Lipids for Protein Monolayer Crystallizations

Author(s): Waleed M. Hussein, Benjamin P. Ross, Michael J. Landsberg, Ben Hankamer and Ross P. McGeary

Volume 13, Issue 14, 2009

Page: [1378 - 1405] Pages: 28

DOI: 10.2174/138527209789055081

Price: $65

Abstract

The use of lipid monolayers to bind and adsorb proteins is an attractive and increasingly important method for generating high localized concentrations of oriented proteins and protein complexes. These bound proteins can be imaged directly, or they may form 2-D crystalline arrays that are amenable to structure determination by single particle analysis or 2-D electron crystallography. 2-D crystals grown by this technique can also be used to initiate the growth of 3-D crystals for X-ray diffraction analysis. Many derivatized lipids have been prepared for use with this technique, incorporating a diverse range of ligands to enable binding to specific proteins. Synthetic lipids containing functionalized head groups that chelate Ni2+ or Cu2+ have also been prepared to bind and orient expressed proteins that contain His-tags. Protein-binding monolayer-forming lipids generally consist of two distinct components: (1) a branched hydrocarbon tail to confer fluidity to the monolayer and (2) a functionalized hydrophilic head group to facilitate binding of protein molecules at the air-water interface. Newer examples of these compounds also incorporate perfluorinated hydrocarbon moieties to confer detergent resistance to these lipids. This review focuses on synthetic approaches to functionalized lipids for protein monolayer crystallizations.


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