Amino activation

Charge diagrams suggest that the 2-amino-5-halothiazoles are less sensitive to nucleophilic attack on 5-position than their thiazole counterpart. Recent kinetic data on this reactivity however, show, that this expectation is not fulfilled (67) the ratio fc.. bron.c.-2-am.noih.azoie/ -biomoth.azoie O"" (reaction with sodium methoxide) emphasizes the very unusual amino activation to nucleophilic substitution. The reason of this activation could lie in the protomeric equilibrium, the reactive species being either under protomeric form 2 or 3 (General Introduction to Protomeric Thiazoles). The reactivity of halothiazoles should, however, be reinvestigated under the point of view of the mechanism (1690). 

The imidazolide group at the amino end of an amino acid is as reactive toward nucleophiles as the imidazolide group at the carboxylic end of an amino acid. If an N-protected amino acid is selected as nucleophile, this method can also be used for peptide synthesis. The amino-activated amino acids, for example N-( 1 -imidazolylcarbonyl)-amino acid esters, are prepared from a-isocyanatocarboxylic acids and imidazole. 

Syntheses of Peptides via Amino-Activation of Amino Acids... 

The possibilities of N-(dialkylphosphoryl)amino acids for the prebiotic syntheses of peptides and polynucleotides have been studied in a series of papers [24,116-122], However, it must be emphasized that the phosphoryl group does not behave as an amino-activating group, the hydrolysis of which would be coupled to peptide bond formation. Actually, further peptide elongation requires the subsequent hydrolysis of the N-terminal phosphoryl group of the ligated product. In the presence of an amino acid ester, dipeptide esters 16 with an unreacted N-phosphoryl protection are formed, support-... 

In this way, penicillin G amidase was first coupled to dextran (see below) with the modified enzyme showing significantly increased thermostability, and this preparation was then immobilized on amino-activated silica gels [49]. 

Coupling of antibody to T2 toxin to amino-activated quartz fibers using cyanogen bromide T2 toxin from Fusarium tricinctum [5]... 

Some further examples involving radiation chemical studies deal with an intramolecular RS -induced hydrogen atom abstraction from a-amino activated C-H bonds. Thus Zhao et report on the formation of C-centered reducing radicals... 

Chitosan, a widely used natural biopolymer, has been studied for the adsorption of various metal ions from dilute solutions. Unfortunately, the inherent properties of chitosan, such as hydrophilicity and metal-binding capability, are often insufficient to meet the requirements of a number of applications. To improve these properties, both chemical and physical modifications of chitosan are required. Thus, Aliquat 336-functionalized chitosan as adsorbent was prepared. In fact, the new chitosan adsorbent can also be described as P-SIL containing quaternary ammonium ionic liquid [23]. Unlike the previous reported structure, the Aliquat 336-functionalized chitosan, which was prepared by acid/base neutralization reaction, consists largely of cations and anions (Fig. 5.12). The structure was so flexible that the adsorption ability could be controlled precisely. Moreover, incorporation of Aliquat 336 into the chitosan backbone could significantly enhance its metal ions extraction ability. It has been shown to have much improved affinity for Pb " than pure chitosan. This may be explained in that the new strategy doesn t reduce the original amino active sites besides, the synergistic effect between cation and anion also contributes to the enhancement of adsorption capabilities. On the other hand, the effort to increase selectivity of the adsorbent for one metal ion over others is to make the adsorbent sterically efficient with that metal ion only. The new chitosan-... 

First, it is possible to excite a chromophore corresponding to the active site, and detennine which modes interact with it. Second, by using UV excitation, the amino acids with phenyl rings (tryptophan and tyrosine, and a small contribution from phenylalanine) can be selectively excited [4], The frequency shifts in the resonance Raman spectrum associated with them provide infomiation on their enviromnent. 

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

The protein folding problem is the task of understanding and predicting how the information coded in the amino acid sequence of proteins at the time of their formation translates into the 3-dimensional structure of the biologically active protein. A thorough recent survey of the problems involved from a mathematical point of view is given by Neumaier [22]. 

Note that the amino-acids, because of their salt-like nature, usually decompose on heating, and therefore seldom have sharp melting-points. Furthermore, all naturally occurring amino-acids are a-amino-acids, and consequently, with the exception of glycine, can exist in optically active forms. 

All the amino-acids of physiological importance are a-amino-acids, e.g. (in addition to the above compounds), alanine or a-amino-propionk acid, CHaCH(NH,)COOH, and leucine or a-amino-Y-dimethyl-rt-butyric acid, (CH,)aCHCH,CH(NHa)COOH, and naturally occurring samples (except glycine) are therefore optically active. 

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

Amino-5 -deoxy-2, 3 -0-isopropylideneadenosine was acylated at N-5 with an activated derivative of the 6-carboxy-2-naphthyl ester of Kemp s acid imide. The resulting molecule possesses self-complementary binding sites, the key feature of replicating molecules that act as templates for their own reproduction. The dimer of this molecule is, however, not very stable K = 630 L mol ). When the two initially mentioned educts are added, a small proportion of the ternary complex is also formed and undergoes a fast, template-catalysed... 

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