Peptides, bonds

A peptide bond is a linkage between the btiilding blocks of proteins called amino acids (shorter strings of linked amino acids are known as peptides). A peptide bond forms when the carboxylic acid group (R-C[0]0H) of one amino acid reacts with the amine group (R-NH2) of another. The resulting molecule is an amide with a C-N bond (R-C(O)-NH-R). 

DNA deoxyribonucleic acid— the natural polymer that stores genetic information in the nucleus of a cell 

The Periodic Table places the symbols of chemical elements, sequenced by atomic number, in rows and colnnms that align similar properties. 

A few thonsand years ago, primitive chemistry focused mostly on converting one snbstance into another. The word chemistry itself is argnably traced to the name of a region of ancient Egypt where such transformation attempts were practiced. Over the centnries, philosophers tried to come to terms with the growing variety of known substances. They postulated the role of fundamental entities that could not be broken down further but formed simple materials when combined. By the time of ancient Greece, Democritus, Leucippus, and Empedocles expounded the nature of matter in terms of constituent elements, the simple substances—earth, air, fire, and 

John Newlands compared elements to musical notes with his law of octaves. As on a scale, every eighth element would share similar properties when arranged by increasing atomic weight. Newlands did not account for exceptions, however, and it was only upon establishment of the Periodic Table that his theory gained credibility. 

Based on stereochemical analysis, it has been proved that in a typical peptide linkage such as shown in the figure, the atoms indicated in bold-type occupy the same plane 

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Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

Where helical secondaiy structures are represented by the cylinder model, the /i-strand. structures are visualized by the ribbon model (see the ribbons in Figure 2-124c). The broader side of these ribbons is oriented parallel to the peptide bond. Other representations replace the flat ribbons with flat arrows to visualize the sequence of the primary structure. 

Ammo acids are carboxylic acids that contain an amine function An amide bond between the carboxylic acid function of one ammo acid and the ammo nitrogen of another is called a peptide bond... 

A dipeptide is a molecule consisting of two ammo acids joined by a peptide bond A tnpeptide has three ammo acids joined by two peptide bonds a tetrapeptide has four ammo acids and so on Peptides with more than 30-50 ammo acids are polypeptides Proteins are polypeptides that have some biological function... 

A key biochemical reaction of ammo acids is their conversion to peptides polypeptides and proteins In all these substances ammo acids are linked together by amide bonds The amide bond between the ammo group of one ammo acid and the carboxyl of another IS called a peptide bond Alanylglycme is a representative dipeptide... 

A major advance was devised by Pehr Edman (University of Lund Sweden) that has become the standard method for N terminal residue analysis The Edman degrada tion IS based on the chemistry shown m Figure 27 12 A peptide reacts with phenyl iso thiocyanate to give a phenylthwcarbamoyl (PTC) denvative as shown m the first step This PTC derivative is then treated with an acid m an anhydrous medium (Edman used mtromethane saturated with hydrogen chloride) to cleave the amide bond between the N terminal ammo acid and the remainder of the peptide No other peptide bonds are cleaved m this step as amide bond hydrolysis requires water When the PTC derivative IS treated with acid m an anhydrous medium the sulfur atom of the C=S unit acts as... 

To direct the synthesis so that only Phe Gly is formed the ammo group of phe nylalanme and the carboxyl group of glycine must be protected so that they cannot react under the conditions of peptide bond formation We can represent the peptide bond for matron step by the following equation where X and Y are amine and carboxyl protecting groups respectively... 

Sections 27 15 through 27 17 describe the chemistry associated with the protection and deprotection of ammo and carboxyl functions along with methods for peptide bond formation The focus m those sections is on solution phase peptide synthesis Section 27 18 shows how these methods are adapted to solid phase synthesis... 

To form a peptide bond between two suitably protected ammo acids the free carboxyl group of one of them must be activated so that it is a reactive acylatmg agent The most familiar acylatmg agents are acyl chlorides and they were once extensively used to couple ammo acids Certain drawbacks to this approach however led chemists to seek alternative methods... 

In one method treatment of a solution containing the N protected and the C protected ammo acids with N N dicyclohexylcarbodiimide (DCCI) leads directly to peptide bond formation... 

The geometry of the peptide bond is planar and the mam chain is arranged m an anti conformation (Section 27 7)... 

Knowing how the protein chain is folded is a key ingredient m understanding the mechanism by which an enzyme catalyzes a reaction Take carboxypeptidase A for exam pie This enzyme catalyzes the hydrolysis of the peptide bond at the C terminus It is... 

An amide linkage between two a ammo acids is called a peptide bond By convention peptides are named and written beginning at the N terminus... 

Selective hydrolysis can be accomplished by using enzymes to catalyze cleavage at specific peptide bonds... 

Section 27 17 Peptide bond formation between a protected ammo acid having a free carboxyl group and a protected ammo acid having a free ammo group can be accomplished with the aid of N N dicyclohexylcarbodiimide (DCCI)... 

In addition to illustrating the mechanics of translation Figure 28 12 is important m that It shows the mechanism of peptide bond formation as a straightforward nude ophilic acyl substitution Both methionine and alanine are attached to their respective tRNAs as esters The ammo group of alanine attacks the methionine carbonyl displac mg methionine from its tRNA and converting the carbonyl group of methionine from an ester to an amide function... 

Chymotrypsin (Section 27 10) A digestive enzyme that cat alyzes the hydrolysis of proteins Chymotrypsin selectively catalyzes the cleavage of the peptide bond between the car boxyl group of phenylalanine tyrosine or tryptophan and some other ammo acid... 

Critical micelle concentration (Section 19 5) Concentration above which substances such as salts of fatty acids aggre gate to form micelles in aqueous solution Crown ether (Section 16 4) A cyclic polyether that via lon-dipole attractive forces forms stable complexes with metal 10ns Such complexes along with their accompany mg anion are soluble in nonpolar solvents C terminus (Section 27 7) The amino acid at the end of a pep tide or protein chain that has its carboxyl group intact—that IS in which the carboxyl group is not part of a peptide bond Cumulated diene (Section 10 5) Diene of the type C=C=C in which a single carbon atom participates in double bonds with two others... 

N terminus (Section 27 7) The amino acid at the end of a pep tide or protein chain that has its a ammo group intact that IS the a ammo group is not part of a peptide bond... 

Peptide (Section 27 7) Structurally a molecule composed of two or more a ammo acids joined by peptide bonds Peptide bond (Section 27 7) An amide bond between the car boxyl group of one a amino acid and the ammo group of another... 

The bond highlighted m yellow is the peptide bond ) Pencyclic reaction (Section 10 12) A reaction that proceeds through a cyclic transition state Period (Section 1 1) A honzontal row of the penodic table Peroxide (Section 6 8) A compound of the type ROOR Peroxide effect (Section 6 8) Reversal of regioselectivity oh served m the addition of hydrogen bromide to alkenes brought about by the presence of peroxides m the reaction mixture... 

Solid phase peptide synthesis (Section 27 18) Method for peptide synthesis m which the C terminal ammo acid is co valently attached to an inert solid support and successive ammo acids are attached via peptide bond formation At the completion of the synthesis the polypeptide is removed from the support... 

Tripeptide (Section 27 1) A compound m which three a ammo acids are linked by peptide bonds... 

Hydrolyzed Vegetable Protein. To modify functional properties, vegetable proteins such as those derived from soybean and other oil seeds can be hydrolyzed by acids or enzymes to yield hydrolyzed vegetable proteins (HVP). Hydrolysis of peptide bonds by acids or proteolytic enzymes yields lower molecular weight products useful as food flavorings. However, the protein functionaHties of these hydrolysates may be reduced over those of untreated protein. 

Deamidation of soy and other seed meal proteins by hydrolysis of the amide bond, and minimization of the hydrolysis of peptide bonds, improves functional properties of these products. For example, treatment of soy protein with dilute (0.05 A/) HCl, with or without a cation-exchange resin (Dowex 50) as a catalyst (133), with anions such as bicarbonate, phosphate, or chloride at pH 8.0 (134), or with peptide glutaminase at pH 7.0 (135), improved solubiHty, whipabiHty, water binding, and emulsifying properties. 

The available free carboxyl groups of the DAS—HMS can be linked via a peptide bond to available primary amine groups onto highly antigenic carriers using a carbodiimide (19). The carriers used in this case were bovine semm albumin (BSA) and poly-L-lysine (molecular weight 150,000 to 300,000). The... 

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