Amino acid interaction with protons

Studies of electrical interactions in proteins, polypeptides, and amino acids started over 60 years ago [1]. To a large extent, electrostatic properties of proteins are determined by the ability of certain amino acids to exchange protons with their environment and the dependence of these processes on pH. The proton occupies a special position as a promoter and iiuxliator in... 

The reaction of various A-tosylated a-amino acids (94) with benzene in concentrated sulfuric acid yielded diphenyl derivatives (95)." The mechanism proposed for the reaction (Scheme 9) involves initial protonation of the carboxyl group to give (96), which suffers decarbonylation to the A-tosyliminium salt (97). This reactive electrophile (97) interacts with benzene to give a monophenyl compound (98) which, via a Friedel-Crafts reaction, interacts with another molecule of benzene to yield the diphenyl compound (95)." Toluene and p-xylene reacted analogously to yield diarylated products. 

The pattern of proton release measured at several pHs for the So-> S,->-S2->S3->-(84) 80 transitions are 1.0 0.0 1.0 2.0 at pH 7.0 or 7.2, 1.0 0.2 1.0 1.8 at pH 6.0 and 1.0 0.8 1.0 1.2 at pH 5.5. The proton release pattern at pH 5.5 may be attributable to a superposition of the intrinsic release and that due to protonation and deprotonation of an amino-acid group (with an apparent pK 5.7) induced by electrostatic interaction with the net charge on an S-state of the OEC. At pH=7, on the other hand, the amino-acid residue is practically deprotonated and cannot contribute to further proton release into the medium. It is also noted that during the So-> S,- S2-)-S3 -> (S4)- So transitions, the oscillation of charges, i.e., the difference between electron abstraction and H release during the transition cycle is 0 0 1 1. Consequently, based on the evaluation of the proton-release stoichiometry, possible water derivatives participating in the various S-states may also be obtained and these are included in the model in Eig. 8 for the period-of-four oscillation of manganese oxidation and proton release. 

THE MECHANISM The mechanism shown outlines the major stages in carboxypeptidase-catalyzed hydrolysis of a peptide in which the C-terminal amino acid is phenylalanine. Proton transfers accompany stages 2 and 3 but are not shown. Only the major interactions of the substrate with the carboxypeptidase side chains are shown although others may also be involved. 

The second part of lanosterol biosynthesis is catalyzed by oxidosqualene lanosterol cyclase and occurs as shown in Figure 27.14. Squalene is folded by the enzyme into a conformation that aligns the various double bonds for undergoing a cascade of successive intramolecular electrophilic additions, followed by a series of hydride and methyl migrations. Except for the initial epoxide protonation/cyclization, the process is probably stepwise and appears to involve discrete carbocation intermediates that are stabilized by electrostatic interactions with electron-rich aromatic amino acids in the enzyme. 

Comparison of solution pH with the pKa of a side chain informs about the protonation state. A unique pKa, termed the standard or model pKa, can be experimentally determined for each ionizable side chain in solution when it is incorporated in a model compound, often a blocked amino acid residue [73] (Table 10-1). In a protein environment, however, the pKa value of an ionizable side chain can substantially deviate from the standard value, due to desolvation effects, hydrogen bonding, charge-charge, charge-dipole, and other electrostatic interactions with the... 

Many times an analyte must be derivatized to improve detection. When this derivatization takes place is incredibly important, especially in regards to chiral separations. Papers cited in this chapter employ both precolumn and postcolumn derivatization. Since postcolumn derivatization takes place after the enantiomeric separation it does not change the way the analyte separates on the chiral stationary phase. This prevents the need for development of a new chiral separation method for the derivatized analyte. A chiral analyte that has been derivatized before the enantiomeric separation may not interact with the chiral stationary phase in the same manner as the underivatized analyte. This change in interactions can cause a decrease or increase in the enantioselectivity. A decrease in enantioselectivity can result when precolumn derivatization modifies the same functional groups that contribute to enantioselectivity. For example, chiral crown ethers can no longer separate amino acids that have a derivatized amine group because the protonated primary amine is... 

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