Switching Antibody Specificity through Minimal Mutation.

Switching Antibody Specificity through Minimal Mutation. Research Abstract Details 

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Switching Antibody Specificity through Minimal Mutation. Abstract Text:

Andrea Piatesi,Caroline Aldag,Donald Hilvert,

Antibody 1E9, which was elicited with a hexachloronorbornene derivative and catalyzes the Diels-Alder reaction between tetrachlorothiophene dioxide and N-ethylmaleimide with high efficiency, was successfully reengineered to bind a range of structurally diverse steroids with nanomolar affinities. Remarkably, two mutations (Leu(H47)Trp/Arg(H100)Trp) out of 36 total sequence differences suffice to switch the selectivity of 1E9 to that of the progesterone-binding antibody DB3. In contrast to the double mutant, which tightly binds multiple steroids with differently configured A-B ring junctions, the individual Leu(H47)Trp and Arg(H100)Trp single mutants both exhibit significantly greater specificity than DB3, preferentially binding 5alpha-pregnan-3beta-ol-20-one (K(d) approximately 5 nM) over other steroids. These findings illustrate how easily differently shaped binding pockets can be created through subtle changes to the same primordial germ line template.

Switching Antibody Specificity through Minimal Mutation. Publishing Authors By Initials

A Piatesi,C Aldag,D Hilvert,

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Switching Antibody Specificity through Minimal Mutation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of molecular biology

VOLUME: 377

Page Numbers: 993-1001

Journal Abbreviation: J. Mol. Biol.

ISSN: 1089-8638

DAY: 2

MONTH: 02

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 2985088

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Grant and Affiliation Information for Switching Antibody Specificity through Minimal Mutation.

AFFILIATION: Laboratory of Organic Chemistry, ETH Zürich, Hönggerberg HCI F 339, CH-8093 Zürich, Switzerland.

Country: England

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MEDLINETA: J Mol Biol

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