Blocked amino acid residue

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... 

Price, S. L., C. H. Faerman, and C. W. Murray. 1991. Toward Accurate Transferable Electrostatic Models for Polypeptides A Distributed Multipole Study of Blocked Amino Acid Residue Charge Distributions. J. Comput. Chem. 12,1187-1197. 

The calculations represented in Figure 8 illustrate the simple fact that atoms occupy space that is, the hard-sphere potential already provides a considerable amount of restriction on the allowed conformations of terminally blocked amino acid residues and hence of oligopeptides built up from such residues. This fact will remain true, to a first approximation, even when more realistic energy functions are introduced. 

Figure 8 Allowed areas of the steric map for various terminally blocked amino acid residues X.45 In area 0, no conformations are allowed. Conformations in areas 1 to 4 are allowed for X = glycine, in areas 2 to 4 for X = alanine, in areas 3 to 4 for higher straight-chain homologs, whereas only area 4 is allowed for X = valine or isoleucine. The circles marked R and L indicate the locations of the standard right-and left-handed a helices on the steric map.

This class of inhibitors usually acts irreversibly by permanently blocking the active site of an enzyme upon covalent bond formation with an amino acid residue. Very tight-binding, noncovalent inhibitors often also act in an irreversible fashion with half-Hves of the enzyme-inhibitor complex on the order of days or weeks. At these limits, distinction between covalent and noncovalent becomes functionally irrelevant. The mode of inactivation of this class of inhibitors can be divided into two phases the inhibitors first bind to the enzyme in a noncovalent fashion, and then undergo subsequent covalent bond formation. 

The conformational preferences of mixed /9-peptides containing both /9 - and /9 -amino acid residues in their sequence differ markedly from that of the corresponding homopolymers consisting exclusively of /9 - or /9 -amino acid residues. Several types of mixed /9-peptides have been investigated including block peptides constructed with triads of /9 -amino acid residues and triads of /9 -amino acid residues (e.g. 93) [104,161], as well as alternating peptides of jf lff type (e.g., 72,... 

Optimal pre-organization of the y-peptide backbone towards the formation of open-chain turn-like motifs is promoted by unlike-y " -amino acid residues. This design principle can be rationalized by examination of the two conformers free of syn-pentane interaction (f and II", Fig. 2.34). Tetrapeptide 150 built from homo-chiral unlike-y -amino acid building blocks 128e has been shown by NMR experiments in pyridine to adopt a reverse turn-like structure stabilized by a 14-mem-bered H-bond pseudocycle [202] (Fig. 2.37 A). 

In today s discussion of the origin of life, the RNA World (Chapter 6) is seen as much more important, and is much better publicized, than the protein world . However, nucleic acids and proteins are of equal importance for the vital metabolic functions in today s life forms. Peptides and proteins are constructed from the same building blocks (monomers), the aminocarboxylic acids (generally known simply as amino acids). The way in which the monomers are linked, the peptide bond, is the same in peptides and proteins. While peptides consist of only a few amino acids (or to be more exact, amino acid residues), proteins can contain many hundreds. The term protein (after the Greek proteuein, to be the first) was coined by Berzelius in 1838. 

The binding sites of most enzymes and receptors are highly stereoselective in recognition and reaction with optical isomers (J, 2 ), which applies to natural substrates and synthetic drugs as well. The principle of enantiomer selectivity of enzymes and binding sites in general exists by virtue of the difference of free enthalpy in the interaction of two optical antipodes with the active site of an enzyme. As a consequence the active site by itself must be chiral because only formation of a diasteromeric association complex between substrate and active site can result in such an enthalpy difference. The building blocks of enzymes and receptors, the L-amino acid residues, therefore ultimately represent the basis of nature s enantiomer selectivity. 

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