Conformational tuning

More yS-amino acids are, apparently, special building blocks within natural (cyclo)peptides and depsipeptides [11]. It is not dear whether Nature aimed at an increase of proteolytic stability or at conformational modification. Chemists, however, followed this example of natural / -amino acid chemistry decades ago and started to modify known a-peptides by substitution of solitary a-amino adds with p-amino acids [12]. One major issue of this synthetic analoging was to increase the proteolytic stability of peptides [13, 14] with regard to peptidases [15]. A second goal was the controlled conformational tuning of cyclo-a-peptides with / -amino acid modifications. 

Pati, S.K., Marks, T.J., Ratner, M.A. Conformationally tuned large two-photon absorption cross sections in simple molecular chromophores. J. Am. Chem. Soc. 123, 7287-7291 (2001)... 

Since the summation in Eq. (12) may be on any subset of atoms, it can be fine-tuned to best suit the problem at hand. The summation may be over the whole molecule, but it is very common to calculate conformational distances based only on non-hydrogen heavy atoms or, in the case of proteins, even based on only the backbone Ca atoms. Alternatively, in a study related to drug design one may consider, for example, focusing only on atoms that make up the pharmacophore region or that are otherwise known to be functionally important. 

Of course, with these alkane spacers rotation is possible about any number ofo-bonds and the convergent conformation is only one of many available to the molecule. This flexibility permits variable distances between opposing carboxyl functions. The price paid for this adjustability is the relatively low probability of any single conformation. The advantage of fine-tuning then, is somewhat offset by the entropic... 

We have found that the communication between Ca2+ sparks and BK channels can be tuned by membrane potential (this study, Herrera et al 2001) and by the accessory / subunit (Brenner et al 2000, Petkov et al 2001). This effect can be accounted for based on the allosteric relationship between the BK channel voltage and Ca2+ sensors, whereby membrane potential depolarization favours a channel conformation that has a higher Ca2+ sensitivity. The /b subunit has a similar role to increase the apparent Ca2+ sensitivity of the a subunit. 

Fine tune tG, F, and L for best resolution while keeping k constant. However, note that high values of tG or low values of F will increase analysis time, may reduce recovery, and can induce conformational changes. 

Pressure was applied in this study to fine tune the lipid chain-lengths and conformation and to select specific lamellar phases. For example, the phospholipid bilayer thickness increases by 1 A/kbar in the liquid-crystalline phase, and up to six gel phases have been found in fully hydrated DPPC dispersions in the pressure-temperature phase space up to 15 kbar and 80 °C, respectively. NMR spectral parameters were used to detect structural and dynamic changes upon incorporation of the polypeptide into the lipid bilayers. 

The understanding of the conformation of dendrimers of different generation as function of concentration, temperature, solvent power, etc., is necessary for further work directed towards the dynamics of these structures as well as to the energy transfer within these molecules. A precise tuning of the conformational freedom is also a prerequisite for all applications discussed so far for dendritic structures [ 1 - 3]. 

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