Peptide unit structure

Peptide units are building blocks of protein structures... 

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.

Conformation of a System of Three Linked Peptide Units. Biopol. 6, 1425-1436. von Carlowitz, S., H. Oberhammer, H. Willner, and J. E. Boggs. 1986. Structural Determination of a Recalcitrant Molecule (S2F4). J. Mol. Struct. 100,161-177. von Carlowitz, S., W. Zeil, P. Pulay, and J. E. Boggs. 1982. The Molecular Structure, Vibrational Force Field, Spectral Frequencies, and Infrared Intensities of CH3POF2. J. Mol. Struct. (Theochem) 87, 113-124. 

Figure 2-15 A stereoscopic alpha-carbon plot showing the three-dimensional structure of favin, a sugar-binding lectin from the broad bean (Viciafaba). In this plot only the a-carbon atoms are shown at the vertices. The planar peptide units are represented as straight line segments. Side chains are not shown. The protein consists of two identical subunits, each composed of a 20-kDa a chain and a 20-kDa 3 chain. The view is down the twofold rotational axis of the molecule. In the upper subunit the residues involved in the front 3 sheet are connected by double lines, while those in the back sheet are connected by heavy solid lines. In the lower subunit the a chain is emphasized. Notice how the back 3 sheet (not the chain) is continuous between the two subunits. Sites for bound Mn2+ (MN), Ca2+ (CA), and sugar (CHO) are marked by larger circles. From Reeke and Becker.112...

More relevant for this section is the use of porphyrins as template for the construction of de novo metalloproteins. Indeed, the attachment of helical peptide units to these templates creates four-helix bundle structures that have been used as an artificial ion channel 2 or a hydroxylase enzymeJ33,34 In these cases, the peptide units were coupled to the template by using the HOSu or the TBTU methods. As illustrated in Scheme 10 starting from 33, formation of the tetrasuccimidyl ester 34 and attachment of the protected peptide unit 35 gives 36 and this is followed by deprotection to 37. 

Fig. 11. The preparation of a four tr-helix structure by cross linking four different peptide units (I, II, III, IV) through disulfide bonds. (Reproduced with the permission of Ref. 19)...

Recently, a modified /J-cyclodextrin was also used as a scaffold in the preparation of a structure that has seven -sheet-forming peptides (45) [38]. Although no structural analysis was reported, this represents the first synthesis of a peptidic architecture with seven adjacent peptide units. 

Finally, Sherman and co-workers [39] recently reported the preparation of a four a-helix structure 46 by attaching the peptide units onto a synthetic bowl... 

They showed that Cu(II) was bound in that position and that the binding process did not influence the tertiary structure. Moreover, the binding of Cu(II) further enhances the structural stability by 1.5 Kcal/mol. In a similar way, the group of Ghadiri [43] has succeeded in preparing a well defined four a-helix structure 50 by forming a Ru(II) complex with four pyridine-modified peptide units 51. 

In biological recognition phenomena, protein-protein interactions are of primary importance. In an attempt to mimic these processes, LaBrenz and Kelly [51] synthesized the peptidic host 64. In this receptor, the dibenzofuran template separates the two peptide units by roughly 10 A and allows for the complexation of a guest peptide (65), as depicted in Fig. 21. The complex first forms a three-stranded, antiparallel /J-sheet that is stabilized by hydrogen bonds, electrostatic interactions, and aromatic-aromatic interactions between the dibenzofuran and the benzamide moieties. This complex can further self associate to form more complex structures. This example shows that structurally defined peptide nanostructures can interfere with biological recognition processes and potentially have therapeutic applications. 

Fig. 22. DeGrado s concept for the development of artificial ion channels. The self-assemblage in a bilayer membrane of an amphiphilic peptide unit generates a hydrophobic oi-helix bundle structure with a polar channel in the middle...

Fig. 1. (a) Formation of a peptide bond, (b) resonance structures of the peptide bond, (c) peptide units within a... 

Fortunately, CD spectroscopy is sensitive not only to the local chirality of the peptide unit, but it also reflects global chirality, that is, the way the chiral units are arranged in space. Therefore, CD can detect different secondary structures within the polypeptide chain. There are four main classes of secondary structures for proteins the a helix, the p sheet, the p turn, and the random coil. In addition, there are also other helix and turn variants which will be discussed. 

---