On the Formation of Peptide Bonds

edited bv RALPHK. BIRDWH~STEL~ Univemily of West Florida Pensamla, FL 32504

textbook forum On the Formation of Peptide Bonds Kiro Stojanoski and Zoran Zdravkovski Institute of Chemistry, Cyril and Methodius University, POB 162, Skopje, Macedonia

Many textbooks, sometimes in a n obvious attempt to simplify the description of some reactions, use very crude models and approximations that implant a wrong image of things and phenomena. A typical example is the explanation for the formation of the peptide bond. In a review of general texts ( l a , l b j currently being used, the following less than accurate statements were found.

Can the reaction proceed in such a way? Is a peptide bond ever formed in this way? To answer these questions the Gibbs free energy change or the equilibrium constant must be calculated. The formation of the simplest dipeptide (glycylglycine)a t 37.5 'C has the following free energy calculations:

:linked together by peptide (ar amide) bonds, which tom a condensation reaction between the carboxyl nino gmup of a second amino acid:

AG" = 483,796 J - 235,141 J

- 2(-366,979 J)

AGO = 15,021J

The equilibrium constant can be estimated using the following formula:

15,021=-

gether by means of dehydratation synthesis, which iino acid molecules by the removal of a molecule of roup of one amino acid and the H- from the amino ,lit off and form water. A -C(OkNH- bond, called a !n the two amino acids.

Other authors also make a mistake in the presentation of the equilibrium reaction for this process (Za, 2b):

Oipeptide

H

0

I

I II I I

H

R,

H-N-C-C-N-C-C-OH

H

H

0

I II I

R,

Peptide gmup

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Journal of Chemical Education

8.314J 310.5K lnKq Kmal 1

The calculated values are probably not very different for other dipeptides (and polypeptides). The positive value of AG" (greater then 10 k J j and the small value ofK,, indicate two things:

.The reaction, as written, cannot take place spontaneously. O n l y negligible amounts of the products are obtained at equilibrium under standard conditions. Indeed the reaction can be made to proceed only in the presence of coupling agents such a s dicyclohexylcarbodiimide, N,N'-carbonyldiimidazole, etc. Historically, Emil Fisher used the corresponding amino acid esters and chlorides for the synthesis of the first synthetic peptides. In living organisms the promoting agents for the reaction are the different enzymes, and the necessary energy is supplied by ATP. This must be borne in mind when describing the formation of the peptide bond. Of the available textbooks a n accurate and acceptable description is given in Stryer's Biochemistry (3): The formation of a dipeptide from two amino acids by loss of a water molecule is shown

below. The equilibrium of this reaction lies on the side of hydrolysis rather than synthesis. Hence the biasynthesis of peptide bands requires an input of free energy, whereas their hydrolysis is thermodynamicallydownhill:

I I

*H,WC-C R,

ti

0

&

+

'0-

I I

*H,WC-C

-

&0 '0-

H

I

0

II

R2

peptide bond

Literature Cited 1. (a1Ebbmg, D. D.;Wrighton, M. S.&mml Chemisfry. 3rd ed.: Howhtm MiRlin: Boston. 1990.0 1012: (bl Metcalfe, H.C.; Williams, J. E.; Caatka, J. F Modem Chemistry. Teacher's Resoureo Book: H d t , Rinehart and wulston: New York, 1986: Worksheet 4 Rofeina, p 13. 2. (a1 Temay, A. L., Jr Confempo~~ry Orgonir Chem. isby; W. B. Saunders: Philadephia, 1979; p 1078; (bl Freifelder, D. Molecular Bblogy; Johnes and Bartlett: Boston, 1987; p 58.

3. Stryer,L. Biochemisny;W. H. Fteeman: New York, 1988; p 22.

Volume 70 Number 2 February 1993

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