Amino acids backbone peptide groups

Figure 4 Retro-inversion of host defense peptides. Synthesis of RI peptides is achieved by substituting o-amino acids at all stereocenters within a peptide and reversal of peptide sequence (RI - R3 in the i-peptide and R3 RI in the Rl-peptide). By rotating the Rl-peptide at 180° it can be seen that the three-dimensional space occupied by the amino acid functional (R) groups is retained in comparison to the i-peptide although the peptide backbone has been reversed.

Figure 2.3 In a polypeptide of five amino acids, the bold black C is the alpha carbon. The amino acids are linked together by a peptide bond (red atoms) linking the carboxylic group of one amino acid to the amino group of the next amino acid. The R group (blueR) can be any sidechain. The Ca-C-N-Ca-C-N-CQ-C-N is the "backbone."...

Abstract This review provides an overview of some of the more recent work directed to exploit radical-based chemistry for the modification of some of Natures most important biomolecules, such as amino acids, peptides, and carbohydrates. Radical reactions are particularly advantageous for carrying out a variety of structural modifications on biomolecules as the reaction conditions are typically compatible with a wide variety of functional groups and solvents. An array of effective synthetic transformations will he discussed including selective side chain and backbone modifications of amino acids and peptides, along with methods for the transformation of carbohydrate substituents, as well as fragmentation and cyclizations reactions for the preparation of either structurally modified carbohydrates or chiral building blocks. 

The N -phthaloyl group (Phth), well known for the preparation of primary amines in the Gabriel synthesis,P was used more extensively as a temporary backbone amine protecting group in the early period of amino acid and peptide chemistry.t The resulting phthalimides ensure exhaustive substitution of the primary amine, i.e. removal of both acidic hydrogens, thus, moderating the nucleophilic character. 

The preceding modifications consist of the addition of special groups to amino acids. Other special groups are generated by chemical rearrangements of side chains and, sometimes, the peptide backbone. For example, certain jellyfish produce a green fluorescent protein (Figure 2.68). The... 

Oxidation of the amino acid moieties in irradiated aqueous systems by reaction with OH is well established for fluid systems, but it is not likely to be encountered in frozen systems. Being a strong oxidant, the OH reacts by electron transfer. It also adds readily to double bonds and abstracts H from C—H, N—H, and S—H bonds, but with lower reaction rate constants. A compendium of rate constants for aqueous solution has been published (52) and a few representative values for amino acids are shown in Table I. As discussed by Simic (53), the predominant sites for reaction in amino acids and peptides can be inferred from these values, which indicate that the ring groups are favored, while abstraction from the peptide backbone is less likely. Hydroxylation of the phenylalanine ring also occurs as was found for the prototype reaction with benzene (54). Formation of phenoxyl radical following OH addition to tyrosine should be similar to the mechanism established for phenol (55) in which elimination of water occurs as is shown in reaction 12 ... 

These agents can be either cyclic peptides with regular amino acids comprising their backbone, or molecules with what, at times, were thought to be non-proteinogenic (non-ribosomal) amino acid backbones. The discoveries in the last few years, particularly by the groups of Ireland and... 

Fig. 3. (a) Chemical stmcture of a synthetic cycHc peptide composed of an alternating sequence of D- and L-amino acids. The side chains of the amino acids have been chosen such that the peripheral functional groups of the dat rings are hydrophobic and allow insertion into Hpid bilayers, (b) Proposed stmcture of a self-assembled transmembrane pore comprised of hydrogen bonded cycHc peptides. The channel is stabilized by hydrogen bonds between the peptide backbones of the individual molecules. These synthetic pores have been demonstrated to form ion channels in Hpid bilayers (71). 

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... 

The dimethoxybenzyl group was used for backbone protection of the pseudopeptides of the form Xaai/r(CH2N)Gly (Xaa = amino acid). It is introduced by reductive alkylation with the aldehyde and NaCNBH3. Acidolysis with TFMSA in TFA/thioanisole is used to remove it from the amine, but the efficiency is dependent upon the peptide sequence. ... 

The long, repetitive sequence of —N—CH-CO- atoms that make up a continuous chain is called the protein s backbone. By convention, peptides are written with the N-terminal amino acid (the one with the free -NH3 1 group) on the left and the C-terminal amino acid (the one with the free -C02 group) on the right. The name of the peptide is indicated by using the abbreviations listed in Table 26.1 for each amino add. Thus, alanylserine is abbreviated Ala-Ser or A-S, and serylalanine is abbreviated Ser-Ala or S-A. Needless to say, the one-letter abbreviations are more convenient than the older three-letter abbreviations. 

FIGURE 4.1. A protein is assembled from amino acids connected to each other by peptide bonds. Each amino acid contributes an identical group to the backbone plus a distinguishing residue (R) as a side chain. 

While the a-helix of L-a-peptides and the (M)-3i4 helix of the corresponding peptides have opposite polarity and helicity (see Section 2.2.3.1), the inserhon of two CH2 groups in the backbone of L-a-amino acids leave these two hehx parameters unchanged, both the a-helix and the 2.614-hehx of the resulting y" -peptides being right-handed and polarized from N to C terminus. In view of these similarities, the y-peptide hehcal fold might prove useful as a template to elaborate functional mimetics of bioachve a-polypeptides. 

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.)...

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