| dc.description.abstract | The results of semiempirical energy calculations on poly(Aib), varying ACO and ?(NC?C) separately and simultaneously, suggest a novel fourfold helical structure as an energetically favourable model for poly(Aib). This novel helical structure, which has been designated as an ??-helix, has 5?1 type of intramolecular hydrogen bonding, pitch around 6 Å and h ? 1.5 Å. Using the Kitaigorodskii potential function (K), the ??-helix (? = 110°, ? = 7°) has the lowest energy. However, using Buckingham 6-exp potential function (B), though the conventional ?-helix (ACO = 0°, ? = 110°) records the lowest energy, the energy difference between ??-helix and conventional ?-helix is just about 1 kcal/monomer unit. Whereas, using K, the energy difference between ??-helix and conventional ?-helix is about 2 kcal/monomer unit in favour of ??-helix. Despite variations in ACO and ?(NC?C), the 3??-helical structure is always found to be less stable than the ?-helical structure. Among 3??-helical conformations, the lowest energy conformation is found for ? = 112°. The energy difference between the best ??- and best 3??-helical conformations is 1.5 kcal/monomer unit using B and 1.2 kcal/monomer unit using K, in favour of ??-helical structure (see Table 4.8). So, for poly(Aib) the conventional ?-helix is not obligatory as suggested earlier (Burgess and Leach, 1973), but an ??-helix and a 3??-helix (? = 112°) are possible structures. The coordinates for the best ??-helix and best 3??-helix are given in Tables 4.9a and 4.9b respectively. The perspective diagrams of these two helices are shown in Figs. 4.8 and 4.9.
The ??-helix is compatible with electron diffraction data of poly(Aib) obtained by Malcolm (1977). The electron diffraction data suggest a helical structure with pitch of 6 Å and have been interpreted by Malcolm (1977) in terms of a 3??-helix. The near meridional reflection of 1.49 Å that is observed in the electron diffraction pattern could be indicative of an ??-helix. It is relevant to point out at this stage the perspective drawing of the best ??-helix (n = 4.00, h = 1.48 Å; ? = –55°, ? = –60°, ? = 7°, ?(NC?C) = 110°) viewed perpendicular to the helix axis. The intramolecular hydrogen bonds (N···O = 3.07 Å, ?H···O = 9.3°) are indicated by dashed lines.
For N-Ac-Aib-Pro-methylamide, a type III ?-turn with C?-exo puckering of the pyrrolidine ring is the most favourable conformation. The conformation with C?-endo puckering is very unlikely. This suggests that Aib-Pro peptides may prove valuable in developing spectroscopic methods for characterizing the puckering state of the pyrrolidine ring by solution studies. On the other hand, for N-Ac-Pro-Aib-NHMe, type III as well as type II ?-turns are stereochemically possible, but type II is energetically more favourable. The puckering of the pyrrolidine ring does not have a significant effect on the backbone conformation of ?-turns in the Pro-Aib sequence. For the Pro-Aib or Pro-X sequence, unlike in the Aib-Pro sequence, the other external forces like crystal packing or solvation rather than intramolecular forces should decide on the state of puckering. This is well supported by the fact that in N-isobutyl-Pro-D-Ala-isopropylamide as reported by Aubry (1976) the ring puckering is C?-endo whereas it is C?-exo in case of the N-Ac-Pro-D-Ala-methylamide reported by Ramaprasad (1978). These points are further summarized in Fig. 5.9 where the variation of conformational energy with ?4 is represented; C?-exo puckering is characterized by positive values of ?4 and C?-endo by negative values. There is only one minimum for the Aib-Pro sequence in the region of positive ?4; there are two for the Pro-Aib sequence (for both type II and type III)-one in the region of positive ?4 and the other in the region of negative ?4. For oligopeptides which contain one or more L-amino acids after the Pro-Aib sequence, it is likely that the molecule prefers the type III ?-turn, so that the ??-helical conformation may propagate with Aib and the next L-amino acid. Such propagation is not possible if the Pro-Aib sequence were to take up the type II ?-turn. This perhaps is the reason for observing Pro-Aib adopting the type III ?-turn in the crystal structures of Boc-Pro-Aib-Ala-Aib-OBz (Smith, 1977) and Z-Aib-Pro-Aib-Ala-OMe (Shamala et al., 1977). Calculations on N-Ac-Aib-Pro-methylester suggest that a large population of these molecules may prefer non-hydrogen bonded conformations. However, a small population of the isomer may adopt hydrogen bonded structures. The chances of occurrence of cis conformers of this molecule are very remote, which is in agreement with experimental studies (Kagaraj, 1980). These studies show that the cis conformer with a cis-Aib-Pro geometry is energetically unfavourable. | |
