Peptide conformational features

Key conformational features of this model believed important for biological potency Include Phe-D-Trp-Lya-Thr and Thr-Phe-Pro-Phe B-turns of Types II and VI, respectively, the latter containing a els peptide bond between Phe and Pro. The model of 3b is very similar with N -methyl alanine replacing proline... 

Much of the information gleaned from studies of ribonuclease S can be applied to studies of far more complex systems. In most cases the receptor-bound form of the peptide will not be known, but the same synthetic modeling approaches can be applied to probe the conformational features of the complex. Two recent examples of the application of this approach to the design of biologically active peptides will be considered in this section. 

In its compact crystal structure, the two opioid tetrapeptide pharmacophores of biphalin are not conformationally equivalent. One tetrapeptide, which has a steric similarity with the delta-selective peptide DADLE, folds into a random coil. The contralateral tetrapeptide, sterically similar to the mu-selective peptide D-TIPP-NH2, exhibits a fairly normal type III (3 bend [4]- These conformational features suggest that under physiological conditions, biphalin may easily bind to these respective opioid receptors. This duality of binding affinity is probably the reason that biphalin is able to interact with all opioid receptor types. 

Nomenclature for conformational features of peptide structure is covered in Chapter 2. 

Introduction the main conformational features of amino acids and peptides... 

Interpretation of spectrometric features of amino acids and peptides and their derivatives has its routine aspects, but the spectra of these compounds also incorporate unique detail that provides specific information about the behaviour of amino acids and peptides in solution. These methods reveal the ways in which groupings within a peptide in solution relate to each other and these details are of major importance in determining the physical and physiological properties of amino acids and peptides. Conformational studies (Chapter 2) and structure determinations for peptides have been the priority targets for investigations by physicochemical methods. 

The primary structure of a peptide is its amino acid sequence. We also speak of the secondary structure of a peptide, that is, the conformational relationship of nearest neighbor amino acids with respect to each other. On the basis of X-ray crystallographic studies and careful examination of molecular models, Linus Pauling and Robert B. Corey of the California Institute of Technology showed that certain peptide conformations were more stable than others. Two arrangements, the a helix and the pleated (3 sheet, stand out as secondary stractural units that are both particularly stable and commonly encountered. Both of these incorporate two important features ... 

Three aspects of solid-state NMR have proved to be fruitful in our initial peptide studies. First, the isotropic chemical shifts in the solid state have led to determination of conformations taken up in the solid (when the structure is not known), and to the correlation of expected chemical shifts with particular conformational features (when the structure is known from diffraction data). 

Three cyclic peptides designed to exemplify different features of peptide conformation have been studied by solid-state NMR ( ), solution NMR (Ifl, j,8) and X-ray diffraction (16). The NMR results described here in brief fonn show a variety of interesting phenomena for these peptides, Cvclo(D-Phe-Pro-Glv-D-Ala-Pro) is a rigid cyclic pentapeptlde which contains in solution... 

Spectra of solid peptides Ccin be used to describe conformational features of the peptides. Of particular utility are the Pro and Cy chemical shifts, which can describe ring geometry or occurrence of cis or trans X-Pro bond conformation. 

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