Amino acids zwitterionic structure

Amino acids, zwitterions, cysteine Peptides, protein structures Enzyme classification Enzyme activity Third hour exam Chemical messengers... 

C-H 0=C hydrogen bonds may inhibit zwitterion formation in the crystalline state. This suggestion has been made on the basis of isonicotinic acid [464], and of nicotinyl glycine [465]. In these crystal structures, the observed C-H 0=C interactions with H 0 distances from 2.35 to 2.66 A and C-ft 0 angles in the range 123 0 to 170° appear to be preferred and suppress the formation of the more common NH 0=0 bonds. Since, however, there is no evidence of this in the amino acid crystal structures, this effect, if real, must be associated with the properties of the pyridine ring. 

Proteins contain, on average, more acceptor than donor sites [596]. Similar proton deficiency in the amino acid zwitterion crystal structures results in the formation of three-center hydrogen bonds rather than in unsatisfied acceptor sites [74] (Part I A, Chap. 2.6). There is less flexibility in the orientation of hydrogen-bond donor and acceptor groups in proteins which would lead to a relatively larger number of unsatisfied acceptor sites. Some of the more unsymmetrical three-center bonds which might have been missed in the survey [596] because of the 3.5 A X - A cut-off limit will also contribute to reduce the number of unsatisfied acceptors in side-chains. 

Internal water molecules tend to form clusters. In general, internal water molecules in protein structures are not found isolated but are assembled in clusters. Their hydrogen-bonding scheme could be derived in actinidin (Fig. 19.13), in lysozyme, and in penicillopepsin, based oh the assumption that water molecules act as double donors and acceptors. In some of the protein structures, which have been analyzed in greater detail, an internal water is associated with three acceptor sites indicating three-center bonding as observed in the amino acid zwitterion crystal structures (see Part IB, Chap. 8). 

C17-0120. In aqueous solution, amino acids exist as zwitterions (German for double ions ), compounds in which internal proton transfer gives a molecule with two charged functional groups. Use Lewis structures to illustrate the proton transfer equilibrium between the uncharged form of glycine (NH2 CH2 CO2 H) and its zwitterion form. 

A Strength of the AFC method is its ability to generate both neutral and zwit-terionic log P estimates for amino acids and other selected zwitterions. The inherent weakness of any estimahon method is predicting structure types not included during method training. The AFC method is no exception. 

Tsai, R.-S. Testa, B. El Tayar, N. Carrupt, P.-A., Structure-lipophilicity relationships of zwitterionic amino acids, J. Chem. Soc. Perkin Trans. 2, 1797-1802 (1991). 

In polar solvents, the structure of the acridine 13 involves some zwitterionic character 13 a [Eq. (7)] and the interior of the cleft becomes an intensely polar microenvironment. On the periphery of the molecule a heavy lipophilic coating is provided by the hydrocarbon skeleton and methyl groups. A third domain, the large, flat aromatic surface is exposed by the acridine spacer unit. This unusual combination of ionic, hydrophobic and stacking opportunities endows these molecules with the ability to interact with the zwitterionic forms of amino acids which exist at neutral pH 24). For example, the acridine diacids can extract zwitterionic phenylalanine from water into chloroform, andNMR evidence indicates the formation of 2 1 complexes 39 such as were previously described for other P-phenyl-ethylammonium salts. Similar behavior is seen with tryptophan 40 and tyrosine methyl ether 41. The structures lacking well-placed aromatics such as leucine or methionine are not extracted to measureable degrees under these conditions. 

Figure 4.1 The zwitterionic structure of two ot-amino acids, and the condensation reaction to form a dipeptide, linked by a peptide bond.

Further efforts in related series afforded structurally similar DPP-4 inhibitors such as acid 13 (E. Parmee, unpublished results), thiazole 14 [35] and cyclopentylglycine 15 (Figure 17.3) [36], Although 15 did not show improved selectivity over DPP-8/9,13 and 14 showed some improvement in selectivity over these counterscreens. Nevertheless, none of these compounds exhibited sufficient selectivity to merit further pursuit zwitterion 13 also possesses low oral bioavailability in rats (F < 1%). Consequently, focus in the a-amino acid series shifted to acyclic derivatives. 

Cation-TT interactions play a crucial role in molecular recognition. For example, Na /K cation interactions with aromatic rings of some amino acids are implicated in the biological functions of specific enzymes and in the selectivity of Na" /K channels. " The same factors are responsible of the relative stability of the charge-solvated vs. zwitterionic structure of amino acids. " ... 

At low pH (acidic solution), an amino acid will exist as the protonated ammonium cation, and at high pH (basic solution) as the aminocarboxylate anion. The intermediate zwitterion form will predominate at pHs between these extremes. The uncharged amino acid has no real existence at any pH. It is ironic that we are so familiar with the terminology amino acid, yet such a structure has no real existence Amino acids are ionic compounds, solids with a high melting point. 

The compounds investigated were the amino acids L-isoleucine, L-leucine, L-valine, and L-a-amino butyric acid. These compounds have similar molecular structures, as shown in Figure 2, and will be referred to throughout the present work as L-Ile, L-Leu, L-Val, and L-a-ABA. Where there is little likelihood of confusion, the designation L- will be omitted. Operations examined included crystallization of He through the addition of hydrochloric acid and through cooling. Under acidic conditions He crystallizes as a hydrochloride salt while in the vicinity of the isoelectric point (pH 5.2) it crystallizes as the neutral zwitterionic... 

When proteins undergo hydrolysis, you wind up with 22 a amino acids, 20 of which are regulcir amino acids and 2 of which are derived amino acids. Amino acids are amphoteric (they possess the characteristics of both acids and bases and can react as either) because both acidic and basic groups are present. An internal acid-base reaction produces a dipolar ion known as a zwitterion (you can see the general structure of one in Figure 16-33). 

Recognition of amino acids has been attempted more frequently with receptors that are likewise zwitterionic in nature (compare 35). Some early studies include the transport of phenylalanine by a merocyanine dye through a liposomal bilayer [53]. Rebek s dicarboxylate-complexing cleft 9 (see Sect. 2) turned out to be a selective (though achiral) binder of trypthophane, phenylalanine, and tyrosine methyl ether [54]. A reasonable structure for a phenylalanine complex of 2 1 stoichiometry, as deduced from NMR studies, is schematically represented in formula 39 [55]. 

This chapter deals with the very important a-amino acids, the building blocks of the proteins that are necessary for the function and structure of living ceils. Enzymes, the highly specific biochemical catalysts are proteins. or-Amino acids are dipolar ions (zwitterions), RCH(N" H,)COO , as is indicated by their crystallinity, high melting point, and solubility in water rather than in nonpolar solvents. The standard (naturally occurring) amino acids are listed in Table 21-1 those marked with an asterisk are essential amino acids that cannot be synthesized in the body and so must be in the diet. They have 1° NHj s except for proline and hydroxyproline (2°). They have different R groups. 

Successive pK a values of the parent acid H4(EDTA) are 2.0, 2.7, 6.2, and 10.3 at room temperature. The first two represent removal of protons from two of the four —COOH groups. It turns out that the other two ioniz-able protons reside on the nitrogens, so that in Na2H2(EDTA) (the form usually supplied by manufacturers) all the carboxyl groups are ionized to — COO- and the two nitrogens are protonated (giving a zwitterion structure, common among amino acids). When H2(EDTA)2- complexes a metal ion, however, all the protons are displaced, and the flexible molecule wraps... 

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