Pseudo C2 symmetry

Figure 13. The two highest occupied Hiickel molecular orbitals for substituted toluenes assuming pseudo-C2 symmetry about the axes shown.

The physical properties of 2 were modified by introduction of polar substituents to improve both antiviral potency and hydrophilicity. These studies led to the discovery of L-689,502 (3) and L-693,549 (4), each bearing a polar, hydrophilic substituent at the para position of the P/ phenyl ring.7-9 Both compounds indeed displayed improved solubilities and antiviral potencies (Table 24.1). An inhibitor with pseudo-C2-symmetry, L-700,417 (5) was designed by rotation of the C-terminal half of 1 around the central hydroxyl-bearing carbon (Figure 24.2).10 Askin and co-workers reported a concise and practical synthesis of compounds 2-5 by diastereoselective alkylation of a chiral amide enolate derived from (I.S, 2/f)-aminoindanol.n This strategy, which efficiently used the cis-aminoindanol platform as chiral auxiliary, is fully detailed later in this chapter. 

In contrast, in the case of haptens the mode of interaction with the paratope is much more restricted because a pocket for the ligand needs to be formed in order to provide a sufficient number of interactions that ensure tight complex formation. This pocket is usually located at fhe interface between the pair of variable domains from the light and heavy chains of the antibody. Hence, a cleft must be formed whose shape is mainly determined by the two CDR-3 loops protruding from fhe Vn and Vl domains, which are related by a pseudo C2-symmetry axis. Because a minimal hydrophobic contact area between Vh and Vl is required in order to maintain fhe non-covalent domain association, the size of this pocket is limited, and many ligands fherefore become just partially buried when bound to an antibody (see Section 8.4). 

As predicted, each subunit of the homotrimer folds into two closely similar domains that are connected by a short linker sequence. Also in line with the earlier hypotheses, the two domains of each subunit are related by pseudo-C2 symmetry. However, contrary to expectation, the E. coli protein is devoid of trigonal symmetry. In the E. coli protein, the N-terminal domain of one subunit and the C-terminal domain of a second subunit form a pseudo-C2-symmetric pair, and the single ( ) active site is located at the interface of that particular domain pair. The evidence for that conjecture is to a significant part based on a comparison between the X-ray structures of the enzymes from E. coli and S. pombe Notably, the E. ro/i protein was crystallized... 

Although the protein environment has no local symmetry properties, the heterocyclic moieties of two substrate analogue molecules are arranged with pseudo-C2 symmetry in the relatively large active site cavity. The topology predicts a pentacyclic adduct whose heterocylic part is the mirror image of the heterocyclic moiety of Compound ( (Figure 19). 

The photosynthetic reaction centres (RCs) are transmembrane protein-pigment complexes that perform light-induced charge separation during the primary steps of photosynthesis. RCs from purple bacteria consist of three protein subunits, L, M and H, and bind four bacteriochlorophylls, two bacteriopheophytins, two quinones, one non-haem iron and one carotenoid. The elucidation at atomic resolution of the three-dimensional structures of the bacterial RCs from Rhodopseudomonas (Rps.) viridis (1) and Rhodobacter (Rb,) sphaeroides (2-4) has provided impetus for theoretical and experimental work on the mechanism of primary charge separation in the RCs. The structures revealed that the cofactors are bound at the interface between the L and M subunits and are organised around a pseudo C2 symmetry axis. However, the structural symmetry does not result in functional symmetry as the electron transfer proceeds only along the L branch (5). 

Of the neurohypophyseal hormones, oxytocin was first crystallized in 1952 (Pierce et ai, 1952) as the flavionate, but the crystals were unsuitable for X-ray analysis. The first of many syntheses of the hormone was carried out by du Vigneaud et ai (1953), and a variety of crystalline salts of oxytocin (Rudko et ai, 1971) and deaminooxytocin analogs (Low and Chen, 1966 Chiu et ai, 1969) have been crystallized. Crystals of deaminooxytocin (and probably also deamino-6-selenooxytocin) crystallize in P2j (two molecules in the asymmetric unit) with pseudo-C2 symmetry. High-resolution X-ray data ( 1 A resolution) on both these forms have been collected, and the structure analysis is being pursued by a combination of isomorphous replacement and vector superposition techniques and direct methods (S.P. Wood, I. J. Tickle, Y. Mascarenhas, T. L. Blundell, and V. Hruby, unpublished results, 1980). 

---