Sequence-Specific Effects

Intramolecular effects play an important role in the modulation of rates and equilibria of CTI in polypeptides. Both local and remote substituents, which are char- 

Changing the chirality at the Ca atom in proline-containing tetrapeptides showed position-dependent thermodynamic and kinetic effects on the CTI [70], Positions adjacent to proline were found to be critical for spontaneous bond rotation. Compared with L-amino acids, D-amino acids in positions preceding and following proline, lead to an increased cis population. Considering the stereospecificity of rate constants Ca chirality affects CTI mainly due to destabilization of the planar trans state relative to the twisted transition state of rotation. 

The propensity of Xaa-Pro moieties to adopt the cis conformation in a pentapep-tide (acetyl-Ala-Xaa-Pro-Ala-Lys-amide) was systematically determined along with CTI-relevant kinetic data [29]. Since there was no evidence for the existence of ordered structure, neither in cis nor in trans isomers of the pentapeptides, substitution-specific differences in CTI parameters can be exclusively attributed to local 

Posttranslational modifications considerably extend the chemical diversity of the building blocks forming polypeptide chains. A good deal of effort has been directed toward understanding how the individual amino acid derivative affects the CTI of neighboring prolyl bonds in peptides and proteins. 

The influence of phosphorylation at the residue preceding the critical proline on the cisitrans ratio is small in terms of the free energy differences AAG° when compared with the unphosphorylated derivative [75], Although, there is a significant increase of the cis trans ratio for the pSer-Pro moiety in oligopeptides, which is reversed for pThr-Pro segments. More importantly, the rate constants for the 

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A closer look at the system, however, does pique curiosity. The initial pH within the chamber is not 7 but 2-3, and the reactions are non-equilibrium, often irreversible, and involve other intermediates that can become important end products. The acidic pH represents a problem in that thiolates, not thiols, are the operative reductants, thus cannot reduce at pH values below their typical i.e. 8-9. This is resolved by proteins, including mfp-6, by sequence specific effects such as flanking cationic groups that reduce the Cys pK, e.g. redox active Cys-59 in DsB-A has a p Tg of 3.5. Several Cys residues in mfp-6 are acidic, but specific p Tg values have yet to be measured. The non-equilibrium, irreversible nature of the oxidation reactions is a particular problem with Dopa and other catechols. Indeed, the chemical fate of catechols in mussel byssus is highly dependent on their location. In the cuticle, the fate of Dopa appears to be tris catecholato-Fe complexes in the thread and plaque core, Dopa forms covalent cross-links after oxidation to quinones, whereas at the plaque-substratum interface, it is some combination of metal chelates and reduced H-bonded Dopa on metal oxide surfaces. The reducing capacity of mfp-6 plays a role in maximizing the latter and is astonishingly sustained, i.e. >21 days. ... 

The amino acid 58 was used in the solid-phase synthesis of sequence-specific DNA binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids <96JACS6141> and it was also reported that the imidazole-acridine conjugate 59 could effectively catalyze the cleavage of t-RNA <96TL4417>. 

SwALLEY, S.E., E.E. Baird, and P.B. Dervan. Effects of y-turn and j8-tail amino acids on sequence-specific recognition of DNA by hairpin polyamides. /. Am. 

A few ex vivo and in vivo studies have been published claiming an antigene (and antisense) effect of mixed purine/pyrimidine sequence PNA [48, 49, 78-80]. However, as pointed out by us in recent reviews [81, 82] these studies lack fundamental controls such as the inclusion of relevant internal standards as a control for sequence-specific non-antigene/antisense effects, thus confirmatory studies are warranted. The in vivo antigene studies from Richelsoris group [79, 83] completely lack a rational basis for the claimed effects. First of all there is no evidence that... 

The effect of deuteration, for the needs of sequence-specific resonance assignments using triple-resonance experiments, was first demonstrated by Bax and co-workers on the 19.7 kDa protein calcineurin B in 1993.56 By replacing the H spin with deuterium, the transverse relaxation time of 13C spin is increased by nearly an order of magnitude due to the 6.5 times smaller gyromagnetic ratio of 2H in comparison to in.52,56 Not surprisingly, deuteration was utilized for the aid of structure determination of several... 

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