Cyclic template

In both cases the rigid cyclic template ensures a highly ordered transition state. 

Searches for a cyclic template to mimic a known ligand... 

The immunodominant portion of the malaria circumsporozoite surface protein contains a tetrapeptide motif (-Asn-Pro-Asn-Ala-), tandemly repeated almost 40 times. Bisang et aft165 incorporated the (I-turn mimetic 131 into the cyclic template 132 (Scheme 48). BALB/c mice... 

Neuropeptide Y (NPY) is a potent inhibitor of neurotransmitter release through the Y2 receptor subtype.[99100] In the search for specific antagonists for the Y2 receptor, the concept of TASP has been applied by attaching four C02H-terminal peptide fragments of NPY (NPY 33-36) via oxime bonds to a cyclic template molecule containing two p-turn mimetics to result in T4-[NPY (33-36)]4, a potent selective antagonist of NPY at the Y2 receptor.1101-102 ... 

To a soln of cyclic template c[-Amhn-Lys-Gly-Lys-Pro-Gly-Lys-Gly-Lys-] -4 HC1 (see Section 13.1.1.1.2) (10 mg, 9 pmol) in DMF (2mL) (at 0°C), DIPEA (7 pL, 39.5 pmol) and (Et0)2CHC02Su (19 mg, 39.5 pmol) were added slowly and the mixture stirred at rt for 3 h. The solvent was removed and the residue redissolved in EtOAc (10 mL). The organic phase was washed with 10% citric acid (3 x), H20 (1 x), and dried (Na2S04). EtOAc was removed and the residue dried in high vacuo yield 7.7mg (56%). The residue was treated with H20/1.2M HC1 (1 1) in order to hydrolyze the tetrakis(diethyl acetal). After 1 h stirring at rt, the solvent was removed in high vacuo. This procedure was repeated three times as the completion of hydrolysis was monitored by analytical HPLC. The residue was purified by HPLC and lyophilized yield 3 mg (66%). 

Scheme 5 Variations of K2K Dendrons and Polyamino, Linear, and Cyclic Templates Lys— Ahx— Lys— ...

The general approach to the structure-based design of NA inhibitors uses the structure of the DANA - NA complex as a starting point and it is based on the development of new classes of lead compounds by using chemically simpler cyclic templates instead of the dihydropyran ring of DANA. 

Scheme 6. Woodward and Doering s opening of cyclic template 19 to provide advanced intermediate 25.

Figure 4. Molecular models of various templates to whidt synthetic peptide epitopes can be ligated. Each template is letravalent providing four points to which peptide epitopes can be attached. The cyclic template b assembled by closure of a disul ide bond within the sequence, the radially branched template shown is assembled by adding a single tier of lysine residues to the alpha and epsilon amino groups of a central lysine residue and the linearly branched template is a simple linear sequence of four lysine residues.

Using a template similar to that described by Mutter etal., Zeng et al. successfully fabricated a pure tetramer by chemical ligation of four 23 amino acid residue peptides using oxime chemistry to the attachment points of the cyclic template. This tetramer was also shown to be more immunogenic than the individual peptide monomers even though the structure of the individual peptide epitopes showed no particular features of conformational structure or stability similar to those reported by Mutter et al. for the TASP that they had assembled. 

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