Linking strategies

Figure 7 A novel, phosphate ester linking strategy [22] was used in the synthesis of phenyl phosphate-containing compound libraries, accomplished in 96-deepwell reaction blocks [23], Rigid, nonpeptide templates (A-group) and pY+3 substituents (B-group) satisfied the diversity sites of the molecules.

The use of the phenyl phosphate group as both a solid support attachment site and a crucial binding element represents what has been referred to as a pharmacophore-linking strategy [26]. We explored a variety of phenyl phosphate tether functionalities to provide resins varying in substitution pattern and in chemical flexibility (Scheme 1 and Table 4) [22]. All phenyl phosphate resins were synthesized in batch quantities of 20 g or more. Resin synthesis began with the addition of either /mnethoxy-benzyl alcohol or benzyl alcohol to commercially available bis(diisopro-pylamino)chlorophosphine, followed by addition of the diversity phenol [(Ri)-OFl, DIAT (diisopropylamino tetrazole)]. Displacement of the... 

Ellman JA, Plunkett MJ. Germanium and silicon linking strategies for traceless solid-phase synthesis. J Org Chem 1997 62 2885-2893. 

With the multifunctional linking strategy either homo- or heterofunctional linking agents can be employed. The homo-approach was widely used in the past for the synthesis of well-defined //-stars with predetermined number and molecular characteristics of arms [163]. New applications of these approaches have been recently reported for the synthesis of A2B, A3B and A2B2 type //-stars. 

Tang, X., Munske, G.R., Siems, W.F., and Bruce, J.E. (2005) Mass spectrometry identifiable cross-linking strategy for studying protein-protein interactions. Anal. Chem. 77, 311-318. 

Hamdan, F. F., Ward, S. D., Siddiqui, N. A., Bloodworth, L. M., and Wess, J. (2002) Use of an in situ disulfide cross-linking strategy to map proximities between amino acid residues... 

Figure 5.17 Noncovalent cross-linking strategies of cyanuric acid functionalized poly-CA to form (a) poly-CA-triazine by using a diaminotriazine cross-linking agent or (b) poly-CA-wedge by using an isophthalamide cross-linking agent.

T. Ruhland, K. Andersen and H. Pedersen, Selenium-linking strategy for traceless solid-phase synthesis Direct loading, aliphatic C-H bond formation upon cleavage and reaction monitoring by gradient MAS NMR spectroscopy, J. Org. Chem., 1998, 63, 9204-9211. 

Builder v.2 Uses the dock and link strategy to link relevant fragments, which satisfy key receptor ligand interactions to form product compounds (81)... 

Plunkett, M. J. Ellman, J. A. Germanium and Silicon Linking Strategies for Traceless Solid-Phase Synthesis, J. Org. Chem. 1997, 62, 2885-2893. 

Fig. 4 Attempt at generating hits through a fragment linking strategy Details of the crystal structures of the active site (see legend to Fig. lc) and selected solvent molecules for the structures of (a) compound 16, (b) compound 17, (c) compounds 16 and 17 and (d) compounds 18 and 17 bound to the active site of Nt-Hsp90...

Ojida A et al (2003) Cross-linking strategy for molecular recognition and fluorescent sensing of a multi-phosphorylated peptide in aqueous solution. J Am Chem Soc 125(34) 10184—10185... 

The same NMR approach by the fragment-linking strategy was used to enhance the activity of a weak inhibitor of p38 MAP kinase. By adding the first one and then a second aromatic ring onto the central five-member heterocylic ring, the activity reached the nanomolar regime [87]. 

---