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New developments in the production and use of stereoselective antibodies
Author(s) -
Hofstetter Heike,
Cary James R.,
Eleniste Pierre P.,
Hertweck Jay K.,
Lindstrom Heather J.,
Ranieri Daniel I.,
Smith Gregory B.,
Undesser L. Pauline,
Zeleke Jessica M.,
Zeleke Tigabu K.,
Hofstetter Oliver
Publication year - 2005
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20099
Subject(s) - stereoselectivity , chemistry , enantiomer , chirality (physics) , amino acid , antibody , stereochemistry , combinatorial chemistry , biochemistry , catalysis , genetics , nambu–jona lasinio model , quark , chiral symmetry breaking , physics , quantum mechanics , biology
This article describes the production of stereoselective antibodies using both classical immunological and modern molecular biological techniques. Stereoselective antibodies against α‐hydroxy acids were raised in rabbits and mice and compared with previously produced anti‐α‐amino acid antibodies. It was found that both types of antibodies combine stereoselectivity with class‐specificity. Sequence analyses revealed that antibodies with opposing stereoselectivities can be formed during the affinity maturation process from a common progenitor or independently using nonhomologous binding sites. For the first time, phage display was employed to obtain stereoselective antibody fragments. The versatility of stereoselective antibodies as chiral selectors was demonstrated by applying them in several immunosensors and in chiral chromatography. A simple, membrane‐based optical sensor allowed detection of enantiomeric impurities at the 1/2,000 level (99.9% ee). Silica‐based antibody chiral stationary phases could be used for enantiomer separation of aliphatic amino acids in standard‐sized columns, while miniaturized columns allowed interfacing with an MS‐detector. Chirality 17:S9–S18, 2005. © 2004 Wiley‐Liss, Inc.