Peptide bond rotation

There has been much discussion about the exact role microwaves play in promoting organic reactions. It is clear that microwaves can activate peptide bond rotation. This may be a factor in the observation J. Am. Chem. Soc. 2008,130, 10048) by Alexander Deiters of North Carolina State University that the rate of the hydrolysis of 24 to 25 by the P-glucosidase CelB from the hyperthermophilic archaeon Pyrococcus furiosus increased by at least four orders of magnitude under microwave irradiation. 

The peptide linkage is usually portrayed by a single bond between the carbonyl carbon and the amide nitrogen (Figure 5.3a). Therefore, in principle, rotation may occur about any covalent bond in the polypeptide backbone because all three kinds of bonds (N——C, and the —N peptide bond) are sin-... 

Peptide bond resonance has several important consequences. First, it restricts free rotation around the peptide bond and leaves the peptide backbone with only two degrees of freedom per amino acid group rotation around... 

FIGURE 6.2 The amide or peptide bond planes are joined by the tetrahedral bonds of the ff-carbon. The rotation parameters are p and Ip. The conformation shown corresponds to clockwise rotation as viewed from Starting from 0°, a rotation of 180° in the clockwise direction ( + 180°) is equivalent to a rotation of 180° in the counterclockwise direction (—180°). (truing G s)... 

There thus is no freedom of rotation about the bond that connects the carbonyl carbon and the nitrogen of a peptide bond. Consequendy, all four of the colored atoms of Figure 3— are coplanar. The imposed semirigidity of the peptide bond has important conse-... 

Figure 3-4. Dimensions of a fully extended polypeptide chain. The four atoms of the peptide bond (colored blue) are coplanar. The unshaded atoms are the a-carbon atom, the a-hydrogen atom, and the a-R group of the particular amino acid. Free rotation can occur about the bonds that connect the a-carbon with the a-nitrogen and with the a-carbonyl carbon (blue arrows). The extended polypeptide chain is thus a semirigid structure with two-thirds of the atoms of the backbone held in a fixed planar relationship one to another. The distance between adjacent a-carbon atoms is 0.36 nm (3.6 A). The interatomic distances and bond angles, which are not equivalent, are also shown. (Redrawn and reproduced, with permission, from Pauling L, Corey LP, Branson PIR The structure of proteins Two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A 1951 37 205.)...

Peptides and proteins are composed of amino acids polymerized together through the formation of peptide (amide) bonds. The peptide bonded polymer that forms the backbone of polypeptide structure is called the a-chain. The peptide bonds of the a-chain are rigid planar units formed by the reaction of the oc-amino group of one amino acid with the a-carboxyl group of another (Figure 1.1). The peptide bond possesses no rotational freedom due to the partial double bond character of the carbonyl-amino amide bond. The bonds around the oc-carbon atom, however, are true single bonds with considerable freedom of movement. 

Figure 1.1 Rigid peptide bonds link amino acid residues together to form proteins. Other bonds within the polypeptide structure may exhibit considerable freedom of rotation.

Figure 2.3 Fragment of polypeptide chain backbone illustrating rigid peptide bonds and the intervening N—Ca and Ca—C backbone linkages, which are free to rotate...

Further examples of catalytic antibodies that are presumed to control rotational entropy are AZ-28, which catalyses an oxy-Cope [3.3]-sigmatropic rearrangement (Appendix entry 13.1) (Braisted and Schultz, 1994 Ulrich et al, 1996) and 2E4, which catalyses a peptide bond isomerization (Appendix entry 13.3) (Gibbs et al., 1992b Liotta et al., 1995). Perhaps the area for the greatest opportunity for abzymes to achieve control of rotational entropy is in the area of cationic cyclization reactions (Li et al., 1997). The achievements of the Lerner group in this area (Appendix entries 15.1-15.4) will be discussed later in this article (Section 6). 

Figure 8 EF-G-catalyzed translocation of the tRNA-mRNA complex within the ribosome, (a) Hybrid state formation and intersubunit rotation. Upon peptide bond formation, the ribosome fluctuates between the classical state and a hybrid state. In the classical state, the tRNAs are bound to the A and P site on both the 308 and 508 subunit. In the hybrid state, the anticodons remain in the A and P site on the 308 subunit whereas the acceptor ends move into the P and E site on the 508 subunit, respectively. 8imultaneously to hybrid state formation, the 308 subunit rotates relative to the 508 subunit as shown on the right site, (b) Kinetic mechanism of EF-G-catalyzed translocation. Upon GTP hydrolysis, unlocking occurs through a ribosomal rearrangement. Only subsequently, tRNA and mRNA movement as well as dissociation of the inorganic phosphate from EF-G take place.

Protein chains are not the sprawling, ill-defined structures that might be expected from a single polypeptide chain. Most proteins are compact molecules, and the relative positions of atoms in the molecule contribute significantly to its biological role. A particularly important contributor to the shape of proteins is provided by the peptide bond itself. Drawn in its simplest form, one might expect free rotation about single bonds, with a variety of conformations possible (see Section 3.3.1). However,... 

With the exception of the terminal residues, every amino acid in a peptide is involved in two peptide bonds (one with the preceding residue and one with the following one). Due to the restricted rotation around the C-N bond, rotations are only possible around the N-C and C -C bonds (2). As mentioned above, these rotations are described by the dihedral angles ( ) (phi) and ]> (psi). The angle describes rotation around the N-C bond / describes rotation around Ca-C—i.e., the position of the subsequent bond. 

The classical methods for detection and quantitation of racemization require analysis of the chiral purity of the product of a peptide-bond-forming reaction. For example, the Anderson test is used to explore a variety of reaction conditions for the coupling of Z-Gly-Phe-OH to H-Gly-OEt (Scheme 6). 9 The two possible enantiomeric tripeptides are separable by fractional crystallization, so that gravimetric analysis furnishes the racemization data. This procedure has a detection limit of 1-2% of the epimerized tripeptide. A modification by Kemp,1"1 utilizing 14C-labeled carboxy components, extends the detection limit by two to three orders of magnitude by an isotopic dilution procedure. The Young test 11 addresses the coupling of Bz-Leu-OH to H-Gly-OEt, and the extent of epimerization is determined by measurement of the specific rotation of the dipeptide product. 

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