Amino Acids Peptides and Proteins

1.3.1 Peptide bonds

While hydrogen bonds are relatively weak, most biological materials including proteins, sugars, fats, and nucleic acids are composed of molecules in which the constituent atoms are linked together by covalent bonds. In covalent bonds, two electrons are shared between the bonding orbitals of the joined atoms. These bonds range in enthalpic energy from about 250 to 400 kJ/mol with the exact value depending on the atoms involved. For example, carbon-carbon bonds have an average energy of 348 kJ/mol, while carbon-nitrogen bonds and carbon-oxygen bonds have energies of 293 kJ/mol and 358 kJ/mol, respectively.

In the biological sciences, there are a number of specially named cova-lent bonds that have achieved this recognition as a consequence of their biological importance. However, no other covalent bond has received the attention of that which joins the amino acid monomers that comprise the polymeric structures known as peptides and proteins. The basis for the extensive study of covalence in protein structure lies in the fact that proteins are primarily responsible for catalyzing the innumerable array of chemical reactions that maintain life. Thus, it is fitting that we begin our consideration of biological molecules with the study of the amino acids and the peptide bond, which is the specially named bond that links amino acids into covalent polymeric structures. These structures include small peptide hormones with fewer than 10 amino acids, up to commonly encountered proteins with an amino acid content ranging from several hundred to more than one thousand. With the 20 different amino acids having an average molecular weight (M.W.) of 120 daltons (Da), the later values correspond to approximate molecular weights of 1200 Da for a 10 amino acid peptide and 60,000 Da for a 500 amino acid protein. One of the largest proteins discovered is titin, a muscle cell protein comprised of 27,000 amino acids with a corresponding M.W. of about 3.2 X 106 Da.

1.3.2 Amino acids

Although there are a large number of amino acids known in nature and in the laboratory, animal proteins are almost exclusively constructed from 20 well-known amino acids. These 20 amino acids are more appropriately referred to as stereospecific, L form, (a) amino acids. Structurally, each alpha carbon unique functional groups

Figure 1.4 Generic structure of amino acids (AA). An H atom, an amino group (NH2), a carboxylic acid group, and an R group, that is different for each amino acid, are covalently bound to a central a-carbon (arrow). The unique R group provides each AA its unique chemical properties.

alpha amino unique functional groups alpha amino

Figure 1.4 Generic structure of amino acids (AA). An H atom, an amino group (NH2), a carboxylic acid group, and an R group, that is different for each amino acid, are covalently bound to a central a-carbon (arrow). The unique R group provides each AA its unique chemical properties.

of them can be characterized as having a hydrogen atom (H), an amino (NH2) group, a carboxylic acid (COOH) group, and a unique functional group (generalized as R) attached to the tetrahedral a-carbon as shown in Fig. (1.4). According to standard chemical nomenclature, the atom next to the carbon atom that bears the molecule's main functional group is known as the a-carbon. In the case of the common amino acids, the main functional group is the dissociable, acidic OH group of the car-boxylic acid. By extension, the next further carbon from the main functional carbon is the b-carbon, and so on.

Other than glycine, all the remaining amino acids have four different substituents attached to the a-carbon, and because of this they can exist in two structurally different chiral or optically active forms, a dextrorotatory (d or +) form, and a levorotatory (l or -) form. The defining feature of chiral molecules is that they are nonsuperimposable mirror images of each other. The l form, which is that found in most human proteins and peptides, rotates plane-polarized light counterclockwise while the d form rotates plane-polarized light in the clockwise direction. These two forms (d and l) are also known as optical isomers or enantiomers.

1.3.3 Polypeptides

Figure 1.5 depicts the structure of the 20 common amino acids grouped according to the chemical functionality of their R groups, which remain unmodified during polypeptide synthesis and provide the characteristic molecular reactivity of the final polymer. In contrast, the invariant car-boxylic acid and amine group associated with the a-carbon react with corresponding groups on linked amino acids to produce the carboxy-amino linkage, which in organic chemistry is known as amide bond and in biology as a peptide bond. The dehydration reaction between alanine and tyrosine to produce water and the peptide bond of alanyl-tyrosine is shown in Fig. 1.6. All peptide bonds are formed via this mechanism. In Fig. 1.6, the four key atoms associated with the peptide bond, and which provide the peptide bond a set of unique structural features, are emphasized by shading. The carbon-nitrogen, or peptide bond in the shaded region has a partial double bond characteristic resulting in all of the atoms in the coo

CH3 alanine (Ala, A)


H3C-ch ch, I 2 ch3 isoleucine

HjC CH3 leucine (Leu, L)

Threonine H3n H3c Cooh

Acid R Groups


1 »







aspartic acid glutamate (Asp, D) Glu, E)



h=n"?7h h3n







1 "

(Cys, C)



R Groups

with Sulfur

(Met, M)





+ 1



chj threonine

3 1 0 HO'CH2

(Thr, T)


(Ser, S)

R Groups

with OH

Cyclic R Group

Basic R Group coo

histidine (His, H)

coo I

Cyclic R Group

Amide R Group



+ 1




| a ch,


1 2 ch2






(Asn, N)

(Gin, Q)

Figure 1.5 The 20 common amino acids. The amino acids are grouped according to the chemical reactivity of their R groups.

shaded region of Fig. 1.6 being rigidly coplanar. Consequently, molecular rotation about the peptide bond is severely limited. This latter steric restriction and the additional steric hindrance donated by bulky or charged R groups are key factors that define the final three-dimensional structure of polypeptides and proteins. It is that native, chemically induced structure that critically defines a polypeptide's biological function o h2n C-oh c h3i nh +




OH Tyrosine


Figure 1.6 Formation of a peptide bond between alanine and tyrosine. The acid function of the amino acid alanine condenses with the a-amine of the amino acid tyrosine to split out a molecule of water resulting in amide, or peptide bond, formation. The shaded region in the dimer highlights the atoms of the peptide bond, all of which remain coplanar as a consequence of electron distribution among the shaded atoms.

as will be outlined in the following chapters. Polypeptides and proteins are presented as critical elements for cell metabolism (Chaps. 3 and 5), cell communication (Chaps. 4 and 6), and for regulation of cell division (Chaps. 7 and 8) and cell development (Chaps. 9 and 10).

Figure 1.7 illustrates the arrangement of four amino acids prior to bonding, with arrows indicating carboxyl and amino groups where dehydration and peptide bond formation can take place. In this illustration, the atoms involved in forming the backbone structure of the polymer and the relationship of the R groups to the nascent backbone become readily apparent.



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