The immune system: genes, receptors, signals : [proceedings] / edited by Eli E. Sercarz, Alan R. Williamson [and] C. Fred Fox.

  • ICN-UCLA Symposium on Molecular Biology
Date:
1974
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: The immune system: genes, receptors, signals : [proceedings] / edited by Eli E. Sercarz, Alan R. Williamson [and] C. Fred Fox. Source: Wellcome Collection.

    48/664 (page 20)
    I. RECHT apparatus constructed by Prof. I.Z. Steinberg and Drs. A. Gafni and J. Schlessinger of our Institute (19,20). RESULTS AND DISCUSSION In all antibody hapten systems hitherto examined only a single chemical relaxation was effected by the temperature jump perturbation. Moreover, in all cases the measured relaxation times depended reciprocally,over an extensive concentration range^ on the free binding sites and haptens (4,6,10). It has already been explained in the introduction that this dependence of is in agreement with a single step binding mechanism. The first series of ligands used for the kinetic mapping of the MOPC 315 site was that of nitro- phenyl ligands where substitutions in the aromatic nucleus have been varied. Pronounced differences were observed in both specific rates of binding (ki2) and dissociation (k2i). However, in this group of derivatives both topological and electron density changes are caused by varying ring substi¬ tutions and it is difficult at the moment to clearly corre¬ late the kinetic data with ligands structure. Thus, main effort was concentrated on varying the side chains attached to the DNP ring. Dinitroaniline derivatives in which one or both amino group hydrogens were substituted by alkyl residues showed the following interesting trend: the changes in the specific rate of binding is decreasing by 50% from the unsubstituted (2,4-dinitroaniline-DNA) 4.8 x 10 mole ~^sec^ to 2.1 x 10^ mole ^sec~^ for the N,N-diethyl dinitroaniline. The chan¬ ges in k2i are much more pronounced, decreasing from 927 sec^ to 373 sec~^ for N,N-dimethyl DNA and rising again to 555 sec~^ for the N,N-diethyl DNA. The data obtained with a more extensive series of normal and branched alkyl subs- tituents on the amino nitrogen is summarized in Table 1. Again we find that both specific rates (k]^2 and k2i) vary, though to a different extent, as a function of the structure of the side chain. In the variation of the reciprocal life¬ time (k2x) of the site-hapten complex, as a function of length and more pronounced on branching of the alkyl side chain/a well defined minimum is observed when a bulky, hydro¬ phobic group is present adjacent to the 1 amine nitrogen of the aromatic ring (table 1 lines 9 and 10). It is remark¬ able to observe how sensitive k2i is to small structural changes. For example for isobutyl and tert butyl side 20