Protein bivalent ligands

Wong M, Greenblatt HM, Dvir H, Carlier PR, Han YF, Pang YP, Silman I, Sussman JL (2003) Acetylcholinesterase complexed with bivalent ligands related to huperzine A experimental evidence for species-dependent protein—ligand complementarity. J Am Chem Soc 125 363-373... 

Halazy, S. (1999) G-protein coupled receptors bivalent ligands and drug design. Expert Opin. Ther. Pat. 9, 431 46. 

Bivalent Ligands Distinguish Between Related Proteins ConA and the Lectin from Dioclea grandiflora... 

Sulfonyl resins (23) have been developed to prepare indoles via a palladium-catalyzed cyclization. Cleavage was carried out with TBAF with excellent yields and purities (85-100%) [78]. Likewise, a library of bivalent ligands (including guanidine, pyridinium and carboxylic and sulfonic acids constituents) for a protein receptor was prepared on nitrobenzenesulfonamide resin 24. Cleavage was achieved with sodium sulfide [79]. 

Wong, D. M., Greenblatt, H. M., Dvir, H., Carlier, P. R., Han, Y. R, Pang, Y. R, Silman, 1., Sussman, J. L. Acetylcholinesterase com-plexed with bivalent ligands related to huperzine a experimental evidence for species-dependent protein-ligand complementarity. J. Am. Chem. Soc. 2003,125,363-373. 

S. Howorka, J. Nam, H. Bayley, and D. Kahne, Stochastic detection of monovalent and bivalent protein-ligand interactions, Angew. Chem. Int. Ed., 43 (2004) 842-846. 

Chemical inducers of dimerization (CID) are bivalent small molecules that bind t vo proteins simultaneously. The purpose of these molecules is to bring the proteins together to induce signal transduction [27]. For brevity, we will limit our discussion to CIDs that directly control transcription. The basic architecture of these systems consists of two chimeric proteins. The first contains a DNA-binding domain (DBD) fused to a ligand-binding domain (LBD) and the second chimera contains an LBD and an activation domain (AD). The small molecule that binds both of these proteins simultaneously induces proximity of the two proteins, resulting in transcription activation (Fig. 8.11). 

The situation is very different for the c-IAP proteins, where only the BIR3 domain displays significant affinity for small molecule ligands. Thus, the only potential new function for bivalent antagonists is the dimerization of c-IAP proteins via the BIR3 domains [37]. The compounds discussed in this section are found in Table 2. 

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