Identification of Cis Trans Isomers

The identification of isomers is as important as their synthesis and purification. The technique to be used for this purpose depends on the species to be analyzed and if it is in solution or in solid state. Without doubt if there are crystals of the material to be analyzed the best way to do it is by X-ray diffraction, but there are other techniques that can be used, such as infrared and Raman spectroscopy, electronic paramagnetic spectroscopy, nuclear magnetic resonance, and electronic...

Cis Trans Isomers of Metal Complexes as Potential Therapeutics

Cis Peptide Bond

Recent advances in medicinal inorganic chemistry have demonstrated significant prospects for the utilization of metal complexes as drugs, presenting a prosperous field for inorganic chemistry. The compounds to be used as drugs have to present low toxicity and high specificity. Some geometrical isomers of different transition metals can present these characteristics and they have been extensively studied, mainly after the discovery by Rosenberg that the cis-diamminodichloroplatinum(II), cis-...

Secondary Structure Formation and CTI

In general, the overall stability of secondary structures results from a number of rather weak noncovalent interactions. These interactions are important determinants of peptide folding motives. Secondary structure formation affects the cis trans equilibrium by favoring either the cis or trans isomer 30,90 . If CTI occurs in secondary structure elements, it should cause peptide backbone reorientation, reconfiguration of hydrogen bonding patterns, hydrophobic interactions, and sol-vatization 91...

Cyclophilins

The prototypical member of the cyclophilins family, cytosolic cyclophilin 18 (Cyp18, CypA) of mammalian cells specifically catalyzes prolyl CTIs but remains inert toward secondary amide peptide bonds 1 . Despite the existence of members of the PPIase class of enzymes in virtually all organisms, some prokaryotic and archaea genomes do not encode enzymes of the cyclophilin family 24 . In larger cyclophilins, additional polypeptide segments complete the full-length proteins. They were found to be...

Phytochromes

Light perception in plants is governed by a series of photoreceptors that can be classified into three groups - the phytochromes, cryptochromes, and phototro-pins. Originally phytochromes were defined as the receptors that were responsible for the red and far-red reversible, plant responses 59 . However they have also been found in bacteria even in nonphotosynthetic bacteria . They are typically homodimers consisting of two polypeptides with a molecular weight of 125 kDa, each containing a...

The Various Isomers Of Cocl2 Nh3

Fig. 14.1 The ComCl2 NH3 4 ion complex A is green and B is violet. To consider Werner's model for coordination compounds totally consistent, it is imperative to show not only the existence of the other isomer for complexes of the CoCl2 NH3 4 type but also for others containing different ligands like Co NO2 2 en 2 , and Co NH3 2 en 2 3 or Co NH3 4 py 2 3 , where the species in the inner coordination sphere of the metal are neutral. Thus, for this purpose by about 1913 approximately two dozen...

Catalytic Mechanism of Peptide Bond Cis Trans Isomerases

Prolyl Isomerase Transition State

Despite the amount of data and the simplicity of the chemical reaction catalyzed, the molecular basis of the catalytic mechanism of PPIases and APIases is still only poorly understood 155 . The considerable degree of amino acid sequence dissimilarity between the subgroups of peptide bond cis-trans isomerases also raises the challenging question of the mechanistic relatedness among the enzymes. At present there is a lack of detailed mechanistic investigations on APIases and multidomain PPIases....

Cyclophilins and FKBPs Similar Molecular Basis for Distinct Catalytic Mechanisms

Cycophlins

The PPIase domains of cyclophilin and FKBPs do not display any similarities whereas members within each subfamily show a high degree of homology in sequence and in three-dimensional structure, suggesting that conservation of the overall shape of the active site and of certain residues is essential for PPIase activity. Moreover, both enzymes feature structural differences from parvulins, in particular Pinl Fig. 12.2 1,9,12 . Fig. 12.2 Ribbon three-dimensional structures of hCyp18 and hFKBP12 and...

Green Fluorescent Protein and Other GFPlike Proteins

Cyclization Peptide Chromophore Gfp

Green fluorescent protein GFP , its mutants and homologs are widely used as biological markers 14-17 . They are particularly useful due to their stability, and the fact that the chromophore is formed in an autocatalytic cyclization that does not require a cofactor. This means that unlike most other bioluminescent reporters GFP fluoresces in the absence of any other proteins, substrates, or cofactors. Furthermore, it appears that fusion of GFP to a protein does not alter the function or location...

Info

Resolution of the structures of several PPIase effector complexes by X-ray crystallography and NMR as well as SAR studies have opened the way to the development of pseudopeptide and peptidomimetic inhibitors which bind PPIases in the 1-50 imol L-1 range. The ketoamide motif redundant to all natural FK506-like macrolides was proposed to be a mimic of the twisted transition state since both carbonyl groups lie in orthogonal planes. Therefore, two independent research groups synthesized Alaw...

Conclusions and Perspectives

Since its introduction in the early 1990s, the concept of pseudoprolines is presently becoming recognized as versatile strategy for the synthesis of difficult peptides. The commercial availability of Fmoc-protected building blocks of the type Fmoc-Xaa-WPro facilitates the introduction of this solubilizing, structure-disrupting dipeptide as a temporary protection technique for Ser, Thr, and Cys. Comparative studies have documented the superiority of the WPro strategy in comparison to other...

Structure and Function of Archaeal Rhodopsin

Halobacteria contain four rhodopsins bacteriorhodopsin, halorhodopsin, sensor-yrhodopsin, and phoborhodopsin Fig. 4.2A 11-17 . Bacteriorhodopsin and halorhodopsin are light-driven ion pumps, which act as an outward proton pump and an inward Cl- pump, respectively. Sensoryrhodopsin and phoborhodopsin are photoreceptors that act to produce attractant and repellent responses in phototaxis, respectively. These four archaeal rhodopsins have similar structures seven helices constitute the...

Pseudoprolines for Modulating Polyproline Helices

Polyproline Helix Ppii

The use of pseudoprolines to induce and lock in oligopeptides in an all-cis conformation was demonstrated on the example of a polyproline I helix 167 . Depending on the experimental conditions, the formation and oligomerization of C2 monoarylated pseudoproline dipeptide building units can be controlled with respect to their configuration and conformation by aromatic stacking interactions 165 . Electrophilically induced cyclic acetyl formation of O-benzyl dipeptide esters e.g. Fmoc-Pro-Thr-OBn...

Isomerization of Phosphatidylcholine in Large Unilamellar Vesicles

Liposomes such as large unilamellar vesicles obtained by extrusion technique LUVET are generally accepted as close models of cell membranes. Figure 6.3 represents a sketch of a vesicle, where it can be seen that the system consists of two distinct compartments - the aqueous and lipid phases. The phospholipid polar heads face the aqueous internal and external phases, whereas the fatty acid chains form the hydrophobic bilayer of the model membrane. Fig. 6.3 Schematic representation of Large...

Natural PPIase Inhibitors and Their Analogs

Cyclophilin Inhibitors

CsA, the most potent peptide inhibitor of many members of the cyclophilin family Ki hCypl8 6 nmol L-1 , is a cyclic ll-mer that contains exclusively hydrophobic amino acids, most of them N-methylated. Moreover, it displays an atypical MeBmt residue which is essential for CsA activity though it does not interact with cyclo-philins. The interaction network that stabilizes Cyp CsA complexes was resolved by NMR and X-ray crystallography more than 10 years ago and, as anticipated, involves five...

Secondary Amide Peptide Bond Cis Trans Isomerases

The dynamics of CTI demonstrate the fundamental similarity between prolyl bonds and secondary amide peptide bonds, making it probable that enzymes exist for the rate acceleration of both types of reactions. The relatively low spontaneous rates indicate the potential importance of CTI of secondary amide peptide bonds as rate-limiting step in protein backbone rearrangements preceding the formation of biologically active proteins. Whereas peptidyl prolyl cis-trans isomerases constitute a...

Parvulins

In 1994, the PPIase family of parvulins was discovered by characterizing the prototypical enzyme Par10 from E. coli 129,130 . This PPIase does not exhibit sequence similarity to either cyclophilins or FKBPs. The mature enzyme, which is 92 amino acids long, is enzymatically active in its monomeric state. A similarly small enzyme has, to the best of our knowledge, not been reported so far. Also, no other organism was reported to possess such a small parvulin. Using a PPIase activity approach, E....

Structural Changes of the Chromophore and Protein upon Retinal Photoisomerization

It is well known that rhodopsin is an excellent molecular switch for converting a light signal to an electric response in the photoreceptor cell. As mentioned in the preceding chapter, the highly efficient photoisomerization of rhodopsin quantum yield 0.67 is assured by the extremely fast CTI of the chromophore that is facilitated by the protein environment 10 . How is such a reaction achieved in protein What is the role of protein environment To understand the role of protein, we need to...

Enzyme Catalyzed Cis Trans Isomerization of Unsaturated Fatty Acid Residues in Bacteria

Cis Trans Fatty Acid

In living cells, membrane properties such as permeability and fluidity have to be flexible to the various conditions therefore there are different mechanisms to effect the necessary modification. Focusing on phospholipids, these mechanisms include changing the saturated unsaturated ratio, changing the chain length or branching of the fatty acid residues, and the phospholipid polar headgroup. There is a strict correlation between the physical properties of biological membranes, going from a...

Imidic Peptide Bonds

As the only example of an imidic peptide bond-forming proteinaceous amino acid, proline has long been recognized to play a unique role in the conformational dynamics and reactivity of native and unfolded polypeptide chains, as well as being a structural determinant 33,34 . There is a stabilizing effect in the cis imide bond preceding proline that can also be found for proline surrogates, which can be introduced by posttranslational modifications of the proline ring and by nonribosomal synthesis...

FK506 Binding Proteins FKBPs

Tetratricopeptide Repeat

Among the PPIases, FKBPs constitute a large family discovered in 1989 7,8 . At this time, the prototypic human enzyme FKBP12 was identified as a FK506 binding molecule the term FKBP includes all proteins that share amino acid sequence homology with FKBP12, although high-affinity FK506 binding is not a common property of FKBP. Our current thinking is that cellular conditions play a decisive role in the affinity of FKBP for FK506, and FK506-mediated enzyme inhibition may occur in a large part of...

Bridged Bicyclic Proline Analogs

Bicyclo[ Hexane

Among the naturally occurring and synthetic bridged bicyclic proline analogs 2228 82-95 , compounds 24 87,96 and 25 86,97,98 have been analyzed for their effects on the amide bond conformation Fig. 11.6 . For example, in model Ac-2,4-MePro-NHMe or Ac-Tyr-2,4-MePro-NHMe the trans conformation of the peptide bond preceding the bridged proline analog is strongly stabilized gt 95 over the cis conformation, making this proline mimetic well suited for a selective stabilization of trans peptide bonds....