Structures of Peptides and Proteins

The primary structure of a protein is the order in which the individual amino acids are sequenced. This tells us little about the shape that the protein will assume in solution, although the primary stmcture naturally determines the secondary, tertiary and even quaternary forms. These amino acid building blocks (Table 11.2) give the key to stmcture and behaviour. The standard three-letter (Glu, Arg, Trp, etc.) and one-letter (E, R, W, etc.) abbreviations for amino acids are also listed their use makes stmctural descriptions more accessible. 

Representations in a stylised diagrammatic form of three proteins (interleukin-l/J, zinc insulin dimers, and the Fc fragment of immunoglobulin) are shown in Fig. 11.3. The nature of the three-dimensional stmcture shows how difficult it is to define proteins in conventional ways, and how they must be considered in a new light as pharmaceutical 

Some of the primary structures are so complex that it is not possible to predict their physicochemical properties, although modern molecular modelling techniques have made great inroads into understanding tertiary stmcture and behaviour.  

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The most stable elements of secondary structure of peptides and proteins are turns, helices, and extended conformations. Within each of these 3D-structures the most commonly found representatives are (3-turns,a-helices, and antiparallel (3-sheet conformations, respectively. y-TurnsJ5 310-helices, poly(Pro) helices, and (3-sheet conformations with a parallel strand arrangement have also been observed, although less frequently. Among the many types of (3-turns classified, type-I, type-II, and type-VI are the most usual, all being stabilized by an intramolecular i <— i+3 (backbone)C=0 -H—N(backbone) H-bond and characterized by either a tram (type-I and type-II) or a cis (type-VI) conformation about the internal peptide bond. In the type-I (3-turn a helical i+1 residue and a quasi-helical 1+2 residue are found, whereas in the type-II (3-turn the i+1 residue is semi-extended and the 1+2 residue is also quasi-helical but left-handed. This latter corner position may be easily occupied by the achiral Gly or a D-amino acid residue. 

SECONDARY STRUCTURES OF PEPTIDES AND PROTEINS method. Amino acid... 

We have noted previously (see Section 2.1) the role played in biochemistry by the thiol disulfide interconversion, and the disulfide unit is a fundamental feature of the structure of peptides and proteins. The sulfur-sulfur bond between two cysteins link remote parts of a peptide chain or cross-link two such chains. Cleavage of these bonds in the hair protein keratin, followed by reoxidation, gives hair its desired shape. 

Amino acids are the building blocks of the polyamide structures of peptides and proteins. Each amino acid is linked to another by an amide (or peptide) bond formed between the NH2 group of one and the C02H group of the other ... 

The primary protein structure of peptides and proteins is the sequence of amino acid residues in the molecule (Figure. 1.7). 

Secondary protein structures are the local regular and random conformations assumed by sections of the peptide chains found in the structures of peptides and proteins. The main regular conformations found in the secondary structures of proteins are the a-helix, the fl-pleated sheet and the triple helix (Figure 1.8). These and other random conformations are believed to be mainly due to intramolecular hydrogen bonding between different sections of the peptide chain. 

The structures of peptides and proteins usually contain numerous amino and carboxylic acid groups. Consequently, water soluble proteins in aqueous solution can form differently charged structures and zwitterions depending on the pH of the solution (see 1.2.2). The pH at which the latter occurs is known as the isoelectric point (p/) of the protein (Table 1.3). The nature of the charge on the structures of peptides and proteins has a considerable effect on their solubility... 

First the general structure and chemistry of the amino acids is presented. Then several methods that can be used to prepare them in the laboratory are discussed. After an introduction to the structure of peptides and proteins, chemical methods that can be used to determine the amino acid sequence in proteins are presented. Next, the synthesis of peptides in the laboratory is introduced. Finally, the three-dimensional structure of proteins and the mechanism of action of enzymes are briefly addressed. 

By convention, peptides are written so that the end with the free amino group, called the N-terminus, is on the left and the end with the free carboxyl group, the C-terminus, is on the right. Because it takes considerable space to show the structure of even a small polypeptide like this one, it is common to represent the structures of peptides and proteins by using the three-letter abbreviation for each amino acid (see Table 26.1). Thus tuftsin, with a threonine N-terminal amino acid, followed by lysine, proline, and, finally, arginine as tire C-terminal amino acid, is represented as... 

The amide bond with its hydrogen-donor and -acceptor properties is critically involved in the onset and stabilization of ordered structures of peptides and proteins as well as in the... 

As illustrated in Scheme 134, both distereoisomers of thiazolidine 535 prepared from commercially available amino acid derivatives 533 and 534 can serve as /3-turn mimetics in the secondary structure of peptides and proteins therefore, they play an important role in many molecular recognition events in biological systems <2002TL1197>. A similar application can be found with thiazoline lactams <1999TL477>. 

MK Green, CB Lebrilla. Ion—molecule reactions as probes of gas-phase structures of peptides and proteins. Mass Spectrom Rev 16 53—71, 1997. 

Furthermore, simulated annealing and other simulation experiments are used to predict 3D structures of peptide and protein structures. Although these methods are still time-consuming processes, they are successfully applied to constraint problems (e.g., for refinement of experimentally obtained data, such as x-ray or NMR structures) [65]. 

Peptides and proteins represent, apart from the nucleic acids, the most important class of compounds governing the basic biochemical principles in nature. During the last hundred years the synthesis of natural and unnatural amino acids as well as peptide synthesis has experienced a breathtaking development. The interest in this process has grown as the knowledge about the relationship between the structure of peptides and proteins and their physiological effects has increased. Nowadays the chemist may refer to a variety of synthetic methods to prepare enantiomerically enriched or pure a-amino acids (for an overview see [1]). Nevertheless, the need for amino acids with a very special substitution pattern often reveals the limits of the established methods. Consequently, the development of new synthetic routes to a-amino acids (and, naturally, also to 8-amino acids, which have enjoyed increased attention over the last years) is playing an important role in the current chemical research. This chapter reviews the application of a special part of radical chemistry in the synthesis and modification of amino acids and peptides, namely reactions that proceed via diradicals. 

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