Scaffold molecules

The main framework is made up of five key modules for chemical library editing, enumeration, conversion, visualization, and analysis. The operations of these functionalities are accomplished by the various applications at the resource layer. For the purpose of illustration, the compound calothrixin B, a secondary metabolite isolated from the Calothrix cyanobacteria (11-13), is used as the scaffold molecule with the variable functional groups Rw] attached (Fig. 18.1). The calothrixins are redox-active natural products which display potent antimalarial and anticancer properties and thus there is interest in probing the physical as well as biological profiles of their derivatives (14). In this exercise, six functional groups have been selected as the building blocks (Table 18.1). 

Wajant H, Henkler F, Scheurich P. 2001. The TNF receptor-associated factor family Scaffold molecules for cytokine receptors, kinases and their regulators. Cell Signal. 13 389-400. 

The influence of these heteroatoms on the reactivity of carbon-scaffolded molecules is briefly reviewed in Section 2.4.1. As one unifying principle, hydrogen-heteroatom bonds break and re-form dynamically in water. In contrast, carbon-heteroatom bonds are rarely broken at standard temperatures unless another bond is formed at the same time. In general, for a chemical reaction to proceed under standard conditions at a rate meta-bolically useful for terran organisms, new bonds must be formed as old bonds are broken, or soon thereafter. 

Ohtsuka, T., Hata, Y, Ide, N., Yasuda, T, Inoue, E., Inoue,T., Mizoguchi, a., Takai, Y. (1999). nRap GEP a novel neural GDP/GTP exchange protein for rapl small G protein that interacts with synaptic scaffolding molecule (S-SCAM). Biochem. Biophys. Res. Commun. 265, 38-44. 

Huntingtin (htt) a causative gene of Huntington s Disease (HD), with its N-terminal CAG trinucleotide repeat expansion correlated with the onset of the disease. Predicted to function as a scaffolding molecule for multiple transporting/transcrip-tional molecules in cytoplasm and nucleus. Inclusion of htt and/or its N-terminal polyglutamine tract have been proposed as a potential mechanism of neurodegeneration in HD. 

Membrane-Associated Guanylate Kinase Inverted-2/Synaptic Scaffolding Molecule... 

A database of scaffold molecules or a single scaffold molecule... 

Attachment points must be specified on both the R-group and the scaffold molecule (Fig. 2.23). 

ChemScreener It is a Java-based platform developed to create diverse but focussed libraries. Tools like SmiLib do not take into account chemical or physico-chemical characteristics of products but rather simply concatenate scaffold molecules and building blocks with single bonds [71]. Often, the libraries created are huge but not chemically meaningful to develop a lead molecule. ChemScreener provides three main modules to use a scaffold extractor library generator, a screener which screens the library for the presence of pharmacophoric, chemophoric and toxico-phoric features. 

Figure 11 The natural oligoantennary glycans of cell surface glycoconjugates, such as high-mannose-type glycoproteins, can be simplified by assembly of the biologically relevant saccharide residues on a branched, multivalent non-carbohydrate scaffold molecule affording a so-called multivalent glycomimetic.

This group of enzymes directs flux into the major classes of plant natural products e.g. polyketides (including flavonoids), alkaloids and terpenes. The initially formed scaffold molecules then enter different branch pathways as precursors for further downstream modifications. 

Scaffolded peptides are also generated through site-selective ligation of three azidoacety-lated peptides to different sites of a scaffolded molecule. For anchoring of peripheral proteins onto cellular membranes an azide labeled diacyl glycerol analogue was reacted with protein kinase C . Click chemistry is also used to produce a monofunctionalized enzyme which retained its reactivity . 

---