Linking amino acids

Proteins are biopolymers formed by one or more continuous chains of covalently linked amino acids. Hydrogen bonds between non-adjacent amino acids stabilize the so-called elements of secondary structure, a-helices and / —sheets. A number of secondary structure elements then assemble to form a compact unit with a specific fold, a so-called domain. Experience has shown that a number of folds seem to be preferred, maybe because they are especially suited to perform biological protein function. A complete protein may consist of one or more domains. 

The structure of any molecule is a unique and specific aspect of its identity. Molecular structure reaches its pinnacle in the intricate complexity of biological macromolecules, particularly the proteins. Although proteins are linear sequences of covalently linked amino acids, the course of the protein chain can turn, fold, and coil in the three dimensions of space to establish a specific, highly ordered architecture that is an identifying characteristic of the given protein molecule (Figure 1.11). 

Whereas the primary structure of a protein is determined by the covalently linked amino acid residues in the polypeptide backbone, secondary and higher... 

Nature has developed exquisite catalysts for a variety of reactions, for example, the hydrolysis of an amide bond. In the absence of a catalyst, amide bonds are extremely stable, making them ideal bonds to link amino acids in order to create... 

Fetterer, R.H. and Rhoads, M.L. (1990) Tyrosine-derived cross-linking amino-acids in the sheath of Haemonchus contortus infective larvae, journal of Parasitology 76, 619-624. 

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.

Y = O-Linked amino acid glycosides Z = /V-a-FMoc-amino acid glycosides... 

The bond linking amino acids together in proteins is known as the peptide bond... 

Amino acid activation Aminoacyl-tRNA synthetase two high-energy bonds (ATP) to link amino acid to tRNA j ... 

Pyridoxal phosphate is a required coenzyme for many enzyme-catalyzed reactions. Most of these reactions are associated with the metabolism of amino acids, including the decarboxylation reactions involved in the synthesis of the neurotransmitters dopamine and serotonin. In addition, pyridoxal phosphate is required for a key step in the synthesis of porphyrins, including the heme group that is an essential player in the transport of molecular oxygen by hemoglobin. Finally, pyridoxal phosphate-dependent reactions link amino acid metabolism to the citric acid cycle (chapter 16). 

Por bafch II fhe dissolution by collagenase was omitted and reduced specimens were hydrolyzed after addition of 0.50 ml demineralized wafer and 0.50 ml concenfrafed HCl (Baker "Insfra-Analyzed"). This enabled fhe HPLC analysis of non-fluorescenf cross-linking amino acids since acid hydrolysis of collagenase-confaining solutions would yield inferfering arfifacfs. 

Keller S, Ghosh AK, Ghosh AK, Turino GM and Mandl I (1984) Separation of the cross-linking amino acids of elastin on thin-layer plates. J Chromatogr 305,461-464. 

Sakura S, Fujimoto D, Sakamoto K, Mizuno A and Motegi K (1982) Photolysis of pyridinoline, a cross-linking amino acid of collagen, by ultraviolet light. Can J Biochem 60, 525-529. 

In Chapter 6, an attempt was made to identify suspect physiological cross-links, tentatively assigned from HPLC dafa, in addition to those already established in literature. Two novel cross-links, denoted chromatographic fractions IV and V-2, were purified from bovine root dentin, and the structure of V-2 was elucidated. During the analysis of human denfin as described in Chapter 5, V-2 appeared below detection level. A peak was observed for IV. Part of the material with the same retention as IV was not retained on cellulose in butanol/acetic acid/water = 4 1 1 (vol.). Co-elution of a non-cross-linking amino acid with IV could therefore not be excluded, and the results were omitted. 

Kleter GA, Damen JJM and Ten Cate JM (1995) Purification of cross-linking amino acids for their analysis in carious dentine. Caries Res 29, 309. 

Due to the vast numbers and rapidity of novel developments in solid-phase synthesis over the past ten years, a number of reports currently found in the literature deal with solid-phase syntheses of lanthionine peptides. There are at least two different approaches to synthesize lanthionine peptides in which the sulfide bond links amino acid halves that are not direct neighbors within the peptide chain (Scheme 10). One obvious approach, method A, is based on the coupling of a preformed, orthogonally protected lanthionine monomer to the N-terminus of a peptide oxime resin. 48 This is then followed by acid-catalyzed cyclization and simultaneous release from the resin during amide bond formation with the C-terminal carboxy group via the peptide cyclization method on oxime resin (see Section 6.73.2.2). The alternative approach is lanthionine formation after peptide synthesis from amino acid derivatives, such as serine and cysteine (method B). 

In a protein the amino acids are joined together in a linear order by amide linkages, also known as peptide bonds. The sequence of the covalently linked amino acids is referred to as the primary level of structure for the protein. In writing the sequence of amino acids in a chain, it is conventional to orient the chain so that the amino acid on the left is the one with a free amino group on its a-carbon, while the last amino acid on the right is the one whose a-carbon carboxylate is free. In other words, the amino- or N-terminus of the peptide chain is written on the left, and the carboxyl-or C-terminus is written on the right. One more convention the term backbone for a protein refers to the series of covalent bonds joining one a-carbon in a chain to the next a-carbon. 

We now turn to polymers of amino acids, the peptides and proteins. Biologically occurring polypeptides range in size from small to very large, consisting of two or three to thousands of linked amino acid residues. Our focus is on the fundamental chemical properties of these polymers. 

The primary stucture of a protein is simply the sequence of amino acids within that protein. These linked amino acids can either curl into an alpha helix or crisscross to form pleated sheets, which are examples of secondary protein structures. The protein chain of amino acids is typically quite long, such that it may have regions of alpha helices and regions of pleated sheets. The larger structure of the protein that includes all the various contours of the whole protein is the tertiary structure. In some instances, two or more tertiary structures will come together to form an even larger complex known as the quaternary structure. 

Like Co(trien(XY) 1+ (Section 13.1.6.2), Co(dien)(XYZ)"+ has been used to bind peptide residues612,680 and, in this case, two linked amino acid groups can be simultaneously coordinated. 

Formation of a dipepetide from two amino acids, (a) Two amino acids, (b) A peptide bond (CO—NH) links amino acids by joining the a-carboxyl group of one with the a-amino group of another. A water molecule is lost in the reaction. It is conventional to draw dipeptides and polypeptides so that their free amino terminus is to the left and their free carboxyl terminus is to the right. The amide plane refers to six atoms that lie in the same plane. (Illustration copyright by Irving Geis. Reprinted by permission.)... 

B. J. Dorgan and R. F. W. Jackson, Synthesis of C-linked amino acid derivatives using organozinc reagents, Synlett, (1996) 859-861. 

An amide bond between the carboxyl group of one amino acid and the amino group of another is called a peptide bond, which links amino acids to one another in peptides and proteins. The amino acid (often abbreviated aa) at one end of the peptide chain will have a free amino group (the N-terminal amino acid), and the amino acid at the other end of the chain (the C-terminal amino acid) will have a free carboxyl group. By convention, we write these structures from left to right starting with the N-terminal end amino acid. 

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