1] FACTORS IN PROTEIN STRUCTURE 19 



amides is significantly more stable than the eis configuration has been sum- 

 marized by Mizushima.^" From infrared absorption studies of amides and 

 TV-substituted amides Badger and Rubalcava^^ concluded that the trans con- 

 figuration may well be stabilized by more than 2 kcal/mole. 



The principal degrees of freedom in the polypeptide chain are the azi- 

 muthal orientations around the N — aC single bond and the aC — C single 

 bond. It was suggested a few years ago by Pauling and Corey^^ ^jj^t six 

 values of the azimuthal angle for each of these single bonds are more stable 

 than other values. Some doubt has been thrown on this conclusion by the 

 observation that the amplitude of the Fourier term with six minima for 

 rotation around the C — N single bond in nitromethane is extremely small, 

 only about 0-003 kcal/mole. At the present time it seems to be wise to allow 

 all azimuthal orientations about the single bonds in the attempted formula- 

 tion of configurations of polypeptide chains. 



There exists now evidence indicating that an additional structural feature 

 for polypeptide chains can be accepted. In their recent review of the configura- 

 tion of polypeptide chains in proteins Pauling and Corey^ stated their opinion 

 at that time of the answer to the question of the orientation of the N — H--0 

 hydrogen-bond axis relative to the O — C axis in the following words: 

 'Although it might be anticipated from consideration of the partial covalent 

 character of the H---0 interaction that the favored orientation of the 

 N — H---0 hydrogen bond about an oxygen atom of an amide group would 

 be in the plane of the amide group and at an angle of about 125° with the 

 C — O bond, there is little evidence that this orientation is at all favored with 

 respect to others, and at the present time it may be assumed that the oxygen 

 atom may form a hydrogen bond in any direction.' 



There exists, however, significant indication that the stable angle between 

 the hydrogen-bond axis and the O — C axis in polypeptides is not about 

 125°, but is close to a straight angle. The evidence supporting this structural 

 feature, an angle of 180° at the oxygen atom, is summarized in the following 

 paragraphs. 



First, all of the known (reasonably well substantiated) structures for poly- 

 peptide chains in nature, including synthetic polypeptides, have the angle 

 approximately 180° for the hydrogen bond at the oxygen atom. These struc- 

 tures include the a-helix,^^ the antiparallel-chain pleated sheet,^^ the parallel- 

 chain pleated sheet,^^ the structure of polyglycine 11,^^ and the several 

 three-chain structures of collagen similar to those suggested by Crick and 

 Rich.16 



In addition, there are several simple peptides and closely related sub- 

 stances in which this angle is nearly 180°. Among these structures are 

 jS-glycylglycine,^'' A^,7V'-diacetylhexamethylenediamine,^^ glycyl-L-tyrosine 

 hydrochloride monohydrate, ^^ and creatinine;^" in all of these structures the 

 deviation from a straight angle is less than 30°. There are also several simple 

 peptides in which the angle at the oxygen atom is as small as 120° to 140° 



