Complex binding phenomena

COMPLEX BINDING PHENOMENA AGONIST AFFINITY FROM BINDING CURVES... 

Complex Binding Phenomena Agonist Affinity from Binding Curves... 

In radioligand binding studies, non-linear Scatchard plots or competition curves that have abnormally steep slopes imply complex binding phenomena, possibly involving multiple receptor types or affinity states. In such cases, the thermodynamic parameters should be separately determined for each receptor type or affinity state. 

Recent developments are pushing towards elucidating complex binding phenomenon between clustered carbohydrate epitopes and multivalent lectins. Ligand valency often results in aggregation, and the kinetic of the process may complicate the ITC measurements.86 For polymers presenting multiple carbohydrate epitopes, such as mucins, it has been proposed that the enhanced affinity observed for these interactions are due to internal diffusion of lectin molecules from epitope to epitope in these multivalent ligands before dissociation.87,88... 

Agonists can produce complex binding profiles due to the formation of different protein species (i.e., ternary complexes with G-proteins). The extent of this phenomenon is related to the magnitude of agonist efficacy and can be used to quantify efficacy. 

Heterodimeric RAR-RXR complexes bind to and regulate target gene transcription from DR1-, DR2-, and DR5-type response elements (see previous sections). Thus, it is conceivable that retinoids could be developed that would selectively activate a RAR RXR complex bound to a DR5 RARE, for example, but not the same complex bound to either DRl or DR2 RAREs, or other, unknown response elements. It has been suggested that such a phenomenon may be caused by the existence of alternative conformations of the RAR-RXR heterodimeric complexes bound to these dif-... 

Metal ion binding phenomenon of cucurbituril was mentioned even in the original report of cucurbituril by Behrend et al. [13] Buschmaim et al. recently studied complexation of alkaline metal ions to cucurbituril by UV-vis spectroscopy (a) Buschmann, H.-J., Cleve, E, A. Schollmeyer, E. Inorg. Chim. Acta 1992,193, 93, (b) Hoffmann, R., Knoche, W., Fenn, C. and Buschmann, H.-J. J. Chem. Soc. Faraday Trans., 1994, 90, 1507. The complex formation constants were measured in the presence of metal salts in the range of 1 X 10 -5 X 10 M. 

SOMC is purely a surface phenomenon where an organometallic complex binds selectively with the surface by covalent (or sometimes ionic or both) bonds. One can then access to its electronic configuration and oxidation state, and this leads to a better understanding of the reaction mechanism. In SOMC, the surface acts as a ligand, which means one can tune the catalytic activity of the organometallic with the surface... 

Recently, the related phenomenon of RNA interference (RNAi) has attracted much attention [5]. RNAi occurs when a short (generally 21 nucleotides in length) double-stranded RNA (dsRNA) catalyticaUy represses the translation of a fully complementary mRNA sequence. The process appears to proceed via a complex formed between the antisense RNA strand and a protein with RNase activity [6]. Upon binding to the target mRNA sequence, the ribonucleoprotein complex initiates cleavage of the mRNA transcript thus preventing translation of intact protein. After dissociation from the truncated mRNAs, the ribonucleoprotein complex is free to act on other intact mRNAs. Such small interfering RNAs (siRNAs) have... 

A second ternary complex reaction mechanism is one in which there is a compulsory order to the substrate binding sequence. Reactions that conform to this mechanism are referred to as bi-bi compulsory ordered ternary complex reactions (Figure 2.13). In this type of mechanism, productive catalysis only occurs when the second substrate binds subsequent to the first substrate. In many cases, the second substrate has very low affinity for the free enzyme, and significantly greater affinity for the binary complex between the enzyme and the first substrate. Thus, for all practical purposes, the second substrate cannot bind to the enzyme unless the first substrate is already bound. In other cases, the second substrate can bind to the free enzyme, but this binding event leads to a nonproductive binary complex that does not participate in catalysis. The formation of such a nonproductive binary complex would deplete the population of free enzyme available to participate in catalysis, and would thus be inhibitory (one example of a phenomenon known as substrate inhibition see Copeland, 2000, for further details). When substrate-inhibition is not significant, the overall steady state velocity equation for a mechanism of this type, in which AX binds prior to B, is given by Equation (2.16) ... 

Many compounds or materials are capable of binding in a reversible fashion to a transition metal complex. If the binding is very strong, or if a large excess of the compound is present, then inhibition is likely to result. Although many examples of this phenomenon have been reported in the literature, only a few have been studied systematically. 

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