O

A few selected examples for such templates or secondary structure mimics are shown in Figure 1.2.2.

Compounds of general formula I were designed to mimic turn structures, which are often key recognition sites in bioactive peptides. Lubell and Hanessian have developed efficient stereo-controlled synthetic routes to azabicycloalkanes I (X, Y = (CH2)n) starting from aspartate or glutamate. These routes provide access to a range of azabicycloalkanes with different side-chains, R, and ring sizes [2]. Some of these systems have been shown to adopt type II and type VI ¿-turn and y-turn conformations. Similar azabicycloalkanes have been synthesized and analyzed by Scolastico and coworkers, starting from substituted proline derivatives [3]. Thia and oxa analogs of I (X = CH2, Y = S or O) have been synthesized by several groups and some derivatives have been shown to adopt ¿-turn conformations [4]. Very recently, an interesting polyhydroxylated thia analog II was synthesized by

iii parallel p-sheet mimic Fig. 1.2.2. Selection of known mimics for major secondary structure elements.

iii parallel p-sheet mimic Fig. 1.2.2. Selection of known mimics for major secondary structure elements.

Tremmel and Geyer from glucuronolactone and cysteine methyl ester and demonstrated to adopt a PII helical conformation in oligomers [5].

Although successful attempts to develop templates for ¿-sheet structures are rare (see also Chapter 2.4), Kemp and coworkers introduced an epindolidione-based template that mimics the central strand of a ¿-sheet by appropriately orienting three hydrogen bonds to enforce an extended conformation on the attached peptide chains, as shown in Figure 1.2.2 with the model system III [6]. Direct attachment of peptide chains to the template leads to the formation of a parallel ¿-sheet mimic, whereas antiparallel ¿-sheet models can be obtained by incorporation of two urea groups for attachment of the peptide chains [7].

0 0

Post a comment