Topological templates

The original concept offered to explain why enzymes exhibit such a high degree of substrate specificity. The active site of an enzyme was viewed as a topological template for a particular reactant hence, there is an enzyme-substrate complementarity . See Induced-Fit Model Ligand-Induced Conformational Change E. Fischer (1894) Ber. 27, 2985. 

Scheme 1 The Concept of Template-Assembled Synthetic Proteins (TASP) Topological Templates Induce Folding of Covalently Attached Peptide Blocks into Predetermined Packing Arrangements 5 13 141...

Scheme 2 Examples of Topological Templates Cyclic Peptides, 14171 Porphyrins,129-301 Cyclodextrins, 281 Calix-arenes131-321...

The use of oxime bond formation with orthogonal protection techniques allows the efficient construction of an antiparallel four-helix-bundle TASP122 (Scheme 19) by condensing amphiphilic peptide blocks, containing aldehyde functions at the C- or N-terminus, to a topological template functionalized with selectively addressable aminooxy acetic acid moieties, t20,22,971... 

Scheme 28 Strategies A-D for the Fixation of Peptide Loop Sequences (L,) to Topological Templates (Tj)[381 A (A )...

Scheme 32 Topological Templates Are Versatile Scaffolds for the Generation of Template-Assembled Peptide Libraries 143 ...

The templates used by Stoddart [39a, b,c] in the syntheses of catenanes and rotaxanes use r- r interactions to enhance both cyclization and interweaving. The template directed cyclization (Scheme 1-9) results in rotaxane formation if the ends of the template 33 are made so bulky that it cannot escape from the macrocycle, and in catenane formation if the two ends of the template are joined to form a macrocycle interlocked with the new macrocycle. The template is an integral part of the final product [39a,d]. Cucurbituril 48 can act as both a linear template and a topological template in the formation of rotaxane, as discussed later (Scheme 1-20). 

Scheme 1-20 Parameters for cucurbituril 48 acting as linear and topological templates.

Template-associated synthetic proteins (TASP), proteins that have been designed and synthesized de novo. Artificial tertiary structures can be constructed by covalent attachment of secondary structure building blocks, e.g., /3-sheets, a-helices, and turns, to a topological template. This results in a non-linear architecture of protein modules that is nevertheless able to mimic native proteins. The combination of different secondary structure motifs in TASP provides, e.g., /Sa/3-structures, helix-bundles, or /3-barrel tertiary structures. The design of TASP makes extensive use of molecular modeling techniques. Solid-phase synthesis and spot synthesis have been used to obtain TASP [G. Tuchscherer, M. Mutter,... 

The use of styrenic block polymers to provide a topological template in producing co-continuous (IPN) blends of thermoplastics. ... 

---