Peptide unit properties

Figure 1.2 shows one way of dividing a polypeptide chain, the biochemist s way. There is, however, a different way to divide the main chain into repeating units that is preferable when we want to describe the structural properties of proteins. For this purpose it is more useful to divide the polypeptide chain into peptide units that go from one Ca atom to the next Ca atom (see Figure 1.5). Each C atom, except the first and the last, thus belongs to two such units. The reason for dividing the chain in this way is that all the atoms in such a unit are fixed in a plane with the bond lengths and bond angles very nearly the same in all units in all proteins. Note that the peptide units of the main chain do not involve the different side chains (Figure 1.5). We will use both of these alternative descriptions of polypeptide chains—the biochemical and the structural—and discuss proteins in terms of the sequence of different amino acids and the sequence of planar peptide units.

A number of clinically useful drugs have been derivatized with a peptide pro-moiety with the view to improve pharmaceutical properties (e.g., solubility) and/or pharmacokinetic behavior (e.g., absorption or targeted delivery). In such cases, and in contrast to the peptides and derivatives and analogues discussed in Sect. 6.3- 6.6, the peptide unit is not part of the pharmacophore. 

This planar, trans peptide unit poses serious limitations example, are proteins with catalytic properties. Their on the shapes proteins can adopt. Understanding the catalytic function depends on the shape adopted alter the... 

Kilbum et al/ described the synthesis and peptide binding properties of some macrocyclic compounds containing a diamidopyridine unit as a carboxylic acid binding site (see Figure 16). Complexation studies in CDClj solution with N-protected (Z or B oc) amino acids or dipeptides were characterized by free association energies of up to 23 kJ/mol, but rather small enantioselectivity (max. AAG 4 kJ/mol). 

The theory of the nonplanar peptide unit has been discussed by several authors, and the results obtained exhibit satisfactory agreement with the experimental chiroptical properties of simple model compounds (Rama-chandran et ai, 1973 Geiger and Wagniere, 1975 Tichy et ai, 1977). 

Hanlon and Klotz (1968) have discussed the use of near-infrared spectroscopy for studying structural problems of biochemistry. In particular, they have considered the equilibrium state of the peptide unit in a number of synthetic polyamino acids (poly-L-alanine, poly-L-leucine, poly-L-methionine, and poly-y-benzyl-L-glutamate) as a function of solvent composition under conditions where the transitions in other physical properties of these polymers have been interpreted as simple peptide, hydrogen-bonded, helix-to-coil transitions. Their spectral data demonstrate that these conversions involve protonated peptide species and are far more complicated than investigators of these processes had assumed. 

L-aspartate (7), y-[2-(9-carbazoIyl)ethyl]-L-glutamate(8), N -[(9-carbazolyl)-carbonyl]-L-lysine (9), and 2-[(9-carbazolyI)ethyl]-L-cysteine (10). No detailed information on the optical rotatory properties of the indicated polymers has been reported, whereas a great deal of attention has been focused on the dichroic absorption properties especially for different samples of poly(8). While the first three polymers are characterized by an a-helix structure in both solution and solid state, poly(lO) may assume antiparallel pleated-sheet and normal antiparallel P-forms. Apparently, the presence of the bulky side group does not substantially affect the conformational structure imposed by the polypeptide backbone. Additionally in concentrated solutions, the cholesterogenic propensity of polypeptides such as those based on L-glutamic acid, L-aspartic acid, and L-lysine is not appreciably influenced by the steric and electronic characteristics of the carbazole moiety anchored via different spacers to the peptide units. 

Proteins are built of peptide units, the amino acids, whose side chains give the structural feature and therefore the functional properties to the molecule. Among the amino acids naturally occurring in proteins, one can distinguish between polar and nonpolar ones. 

One should note the difference between amino acid residues which refers to —NH—CHR—CO and peptide units which refers to —CHR—CO—NH— (Fig. 2.2). The peptide unit corresponds to the properties of the peptide bond it has a partial double-bond character because of the existence of two resonance forms (Fig. 2.3a) which strongly restricts the possibility of rotation around the C—N bond. Consequently, this group is generally planar however, deviations from planarity of the peptide bond have been observed. An evaluation of conformational energy calculations indicated deviation of only 1-3° in low energy minima of Gly-Gly, but as much as 10° in Gly-Pro (Zimmerman and Scheraga, 1976). 

Properties and Structure. a -Acid glycoprotein (a -AGP) has a molecular mass of about 41,000 and consists of a peptide chain having 181 amino acid residues and five carbohydrate units (14,15). Two cystine disulfide cross-linkages connect residues 5 and 147 and residues 72 and 164. The carbohydrate units comprise 45% of the molecule and contain siaUc acid, hexosamine, and neutral hexoses. In phosphate buffer the isoelectric point of the... 

Interleukin-1 (IL-1) produced by monocytes and several other cell types [70, 146] has a wide array of biological properties, including T cell activation and inflammatory interactions with muscle, liver, fibroblasts, brain and bone [70, 146], IL-1, both natural and recombinant, has been shown to release histamine from human basophils and from human adenoidal mast cells [70,146,151] and this release was abolished by an IL-1 antibody. However, the average release produced by 10 units of IL-1 was less than 20% and there was considerable variability between populations of basophils in the extent of histamine release. Moreover, the secretory response elicited was quite slow (within 15 min) compared with that of other peptides [151]. Desensitization of the basophils by anti-IgE serum had no effect on the subsequent IL-1 response, suggesting different mechanisms of action [ 151], as has been the case with other peptides. Interestingly, the portion of the IL-1 molecule that is responsible for its immu-nostimulatory activity appears to be separate from that portion responsible for its proinflammatory effects [152]. However, that portion of the molecule responsible for eliciting basophil and mast-cell histamine release has not as yet been defined. 

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