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Comparison of phosphonate transition state analogs for inducing catalytic antibodies and evaluation of key structural factors by an ab initio study

✍ Scribed by Hiroyuki Kakinuma; Kazuko Shimazaki; Naoko Takahashi; Kyoko Takahashi; Shigeo Niihata; Yoshiko Aoki; Katsumi Hamada; Hajime Matsushita; Yoshisuke Nishi


Book ID
104209255
Publisher
Elsevier Science
Year
1999
Tongue
French
Weight
861 KB
Volume
55
Category
Article
ISSN
0040-4020

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✦ Synopsis


The relation between the structure of haptens and the esterolytic activities of antibodies was investigated.

We synthesized two phenylalanine analogs, the negatively charged phosphonate derivative 1 and the neutral pbosphonamidate derivative 2. Seventeen out of 41 monoelonal antibodies generated against the hapten 1 hydrolyzed the relevant phenylalanine ester R-12. On the contrary, none of 27 monoclonal antibodies generated against the hapten 2 had catalytic activity. An ab initio study of the structural and electronic properties of the modeled haptens showed that the value of the negative electrostatic potential around the phosphonyl oxygen was an important factor affecting the induction of esterolytic antibodies.