When compared to the D2-like antagonist [3H] spiperone, competition binding for agonists like dopamine and apomorphine were 2 10-fold more potent with [3H] A-369508, while the antagonists clozapine, haloperidol and L-745870 bind with similar affinity to both ligands.
Ang-1 and Ang-2 are antagonistic ligands that bind with similar affinity to the extracellular domain of the Tie2 receptor, which is almost exclusively expressed by endothelial cells.
It was demonstrated that one group of antimitotic agents, vinca alkaloids, bind with similar affinity to all β-tubulin isotypes [ 12], thus suggesting for therapy with vinorelbine, vinblas-tine, or vincristine that tubulin isotype levels are incidental for efficacy.
Interestingly, it is reported that their affinities to ligands are different: AHK2 and AHK4/ WOL1/ CRE1 bind with similar affinity to tZ as well as iP, while AHK3 has less affinity to iP than to tZ [ 4, 50].
However, one group of antimitotic agents, the vinca alkaloids, was shown to bind with similar affinity to all tubulin isotypes [ 12], suggesting that alterations in drug binding affinity is unlikely to be the cause of drug resistance.
It has previously been shown qualitatively that all of the two domain constructs from cluster II of LRP, except CR9 and CR10, can bind with similar affinity to domain D3 from RAP when they are expressed as fusion proteins with ubiquitin [ 19].
These experiments revealed two distinct nucleotide binding sites; AMP, ADP, and ATP bind with similar affinities at a tight site (Kd,I for ADP ∼80 μM) and at a weaker one (Kd,II for ADP ∼800 μM).
Two of these paralogs, SP3 and SP4, bind with similar affinities to the SP1 binding consensus, regulating transcription in a complex manner through competitive binding to the same sites (Philipsen and Suske 1999; Suske 1999; Bouwman and Philipsen 2002; Wierstra 2008).
Moreover, the DNA-binding domains of human and mouse PPARα are completely homologous [70], suggesting that they should bind with similar affinities to the megalin PPREs.
The latter observation was unexpected given the parental compound JQ1 is a pan-BET inhibitor and our PROTACs bind with similar affinities to BET bromodomains.
